Antibacterial compounds and methods for use

ABSTRACT

The present description relates to compounds and forms and pharmaceutical compositions thereof and methods for use thereof to treat or ameliorate bacterial infections caused by wild-type and multi-drug resistant Gram-negative and Gram-positive pathogens.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is the National Stage of International Application No.PCT/US2012/052898, filed Aug. 29, 2012, which claims the benefit of U.S.Application No. 61/528,576, filed Aug. 29, 2011, the entire contents ofwhich are incorporated by reference herein.

FIELD OF THE INVENTION

The present description relates to compounds and forms andpharmaceutical compositions thereof and methods of using such compounds,forms or compositions thereof for treating or ameliorating a bacterialinfection. More particularly, the present description relates tocompounds and forms and pharmaceutical compositions thereof and methodsof using such compounds, forms or compositions thereof for treating orameliorating a bacterial infection, or for treating or ameliorating amulti-drug resistant (MDR) bacterial infection.

BACKGROUND OF THE INVENTION

Currently marketed antimicrobial agents inhibit bacterial DNA synthesisby acting on the two key enzymes of DNA gyrase and topoisomerase IV(see, Mitscher, L. A. Bacterial topoisomerase inhibitors: quinolone andpyridone antibacterial agents, Chem. Rev. 2005, 105, 559-592; Hooper, D.C.; Rubinstein, E. Quinolone antimicrobial agents/edited by David C.Hooper and Ethan Rubinstein; or De Souza, M. V. New fluoroquinolones: aclass of potent antibiotics. Mini. Rev. Med. Chem. 2005, 5 (11),1009-1017).

The DNA gyrase and topoisomerase IV enzymes are both type IItopoisomerases, consisting of two protein subunits active asheterodimers (A₂B₂). The ATPase domain resides on one polypeptide (GyrBin DNA gyrase, ParE in topoisomerase IV), while the DNA cleavage corelies on a second polypeptide (GyrA in DNA gyrase, ParC in topoisomeraseIV). Current therapies, including the aminocoumarin novobiocin, functionas competitive inhibitors of energy transduction of DNA gyrase bybinding to the ATPase active site in GyrB (see, Maxwell, A. Theinteraction between coumarin drugs and DNA gyrase. Mol. Microbiol. 1993,9 (4), 681-686; Flatman, R. H.; Eustaquio, A.; Li, S. M.; Heide, L.;Maxwell, A. Structure-activity relationships of aminocoumarin-typegyrase and topoisomerase IV inhibitors obtained by combinatorialbiosynthesis. Antimicrob. Agents Chemother. 2006, 50 (4), 1136-1142).

In contrast, the nalidixic acid, ciprofloxacin and moxifloxacinpreferentially bind these enzymes at the cleavage core (GyrA and ParC)and prevent decatenation of replicating DNA (see, Hooper, D. C.Quinolone mode of action. Drugs 1995, 49 Suppl 2, 10-15). Although firstsite resistance mutations generally occur in gyrA, mutations in gyrBalso have been shown to reduce susceptibility to quinolones (see,Yoshida, H.; Bogaki, M.; Nakamura, M.; Yamanaka, L. M.; Nakamura, S.Quinolone resistance-determining region in the DNA gyrase gyrB gene ofEscherichia coli. Antimicrob. Agents Chemother. 1991, 35 (8),1647-1650).

Bacterial DNA synthesis inhibitors (e.g., fluoroquinolones) have beenused to treat primarily Gram-negative infections and have historicallyachieved outstanding clinical outcomes (see, Emmerson, A. M.; Jones, A.M. The quinolones: decades of development and use. J. AntimicrobialChemotherapy, 2003, 51 (S1), 13-20). A wealth of knowledge exists forthe quinolone class of compounds (see, Hooper, D. C.; Rubinstein, E.Quinolone antimicrobial agents/edited by David C. Hooper and EthanRubinstein), including bioavailability, tissue distribution, PK/PDrelationships and photoxicity. Structurally, quinolone antibioticspossess a bicyclic (ciprofloxacin and moxifloxacin) or tricyclic ringstructure (levofloxacin) with an aryl side chain containing an acyclicring incorporating an amine functionality.

Other ring structures such as the 2-pyridones (monocyclic andbicyclic)(see, Chu, D. T. Recent progress in novel macrolides,quinolones, and 2-pyridones to overcome bacterial resistance. Med. Res.Rev. 1999, 19 (6), 497-520), quinazolinediones (see, Ellsworth, E. L.;Tran, T. P.; Showalter, H. D.; Sanchez, J. P.; Watson, B. M.; Stier, M.A.; Domagala, J. M.; Gracheck, S. J.; Joannides, E. T.; Shapiro, M. A.;Dunham, S. A.; Hanna, D. L.; Huband, M. D.; Gage, J. W.; Bronstein, J.C.; Liu, J. Y.; Nguyen, D. Q.; Singh, R. 3-aminoquinazolinediones as anew class of antibacterial agents demonstrating excellent antibacterialactivity against wild-type and multidrug resistant organisms. J. Med.Chem. 2006, 49 (22), 6435-6438; and, Tran, T. P.; Ellsworth, E. L.;Stier, M. A.; Domagala, J. M.; Hollis Showalter, H. D.; Gracheck, S. J.;Shapiro, M. A.; Joannides, T. E.; Singh, R. Synthesis andstructural-activity relationships of 3-hydroxyquinazoline-2,4-dioneantibacterial agents. Bioorg. Med. Chem. Lett. 2004, 14 (17), 4405-4409)and tricyclic isoquinolones have been described in the literature.

Though some of these molecules, such the 2-pyridone and 4-pyridones(e.g., Ro-13-5478), isoquinolones and quinazolinediones have progressedto the late preclinical stage, none have reached the market. In the1980s, monocyclic 2-pyridone and 4-pyridones were reported to inhibitDNA gyrase (see, Georgopapadakou, N. H.; Dix, B. A.; Angehrn, P.; Wick,A.; Olson, G. L. Monocyclic and tricyclic analogs of quinolones:mechanism of action. Antimicrob. Agents Chemother. 1987, 31 (4),614-616).

The monocyclic 4-pyridone class of molecules generally exhibited pooractivity against quinolone-resistant (quin^(R)) strains, possessedattendant CNS side effects, and in most cases, had only limited in vivoefficacy. Recent studies on monocyclic-4-pyridone analogs (see, Laursen,J. B.; Nielsen, J.; Haack, T.; Pusuluri, S.; David, S.; Balakrishna, R.;Zeng, Y.; Ma, Z.; Doyle, T. B.; Mitscher, L. A. Further exploration ofantimicrobial ketodihydronicotinic acid derivatives by multiple parallelsyntheses. Comb. Chem. High Throughput. Screen. 2006, 9 (9), 663-681)demonstrate that these compounds elicit cross-resistance tociprofloxacin and possess poor antibacterial activity against E. coli.

More recently, antibacterial spiro-tricyclic barbituric acid derivatives(QPT-1) (see, Miller, A. A.; Bundy, G. L.; Mott, J. E.; Skepner, J. E.;Boyle, T. P.; Harris, D. W.; Hromockyj, A. E.; Marrotti, K. R.; Zurenko,G. E.; Munzner, J. B.; Sweeney, M. T.; Bammert, G. F.; Hamel, J. C.;Ford, C. W.; Zhong, W-Z.; Graber, D. R.; Martin, G. E.; Han, F.; Dolak,L. A.; Seest, E. P.; Ruble, J. C.; Kamilar, G. M.; Palmer, J. R.;Banitt, L. S.; Hurd, A. R.; Barbachyn, M. R. Discovery andcharacterization of QPT-1, the progenitor of a new class of bacterialtopoisomerase inhibitors. Antimicrob. Agents Chemother. 2008, 52 (8),2806-2812; and, Ruble, J. C.; Hurd, A. R.; Johnson, T. A.; Sherry, D.A.; Barbachyn, M. R.; Toogood, P. L.; Bundy, G. L.; Graber, D. R.;Kamilar, G. M. Synthesis of (−)-PNU-286607 by asymmetric cyclization ofalkylidene barbiturates. J. Am. Chem. Soc. 2009, 131 (11), 3991-3997),inhibitors possessing a tetrahydroindazole and piperidine motif and a6-methoxyquinoline moiety (e.g., NXL101 and GSK299423) (see, Black, M.T.; Stachyra, T.; Platel, D.; Girard, A. M.; Claudon, M.; Bruneau, J.M.; Miossec, C. Mechanism of action of the antibiotic NXL101, a novelnonfluoroquinolone inhibitor of bacterial type II topoisomerases.Antimicrob. Agents Chemother. 2008, 52 (9), 3339-3349; Bax, B. D.; Chan,P. F.; Eggleston, D. S.; Fosberry, A.; Gentry, D. R.; Gorrec, F.;Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs, M.; Huang, J.; Jones,E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E. W.; Saunders, M. R.;Singh, O.; Spitzfaden, C. E.; Shen, C.; Shillings, A.; Theobald, A. J.;Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N. Type IIA topoisomeraseinhibition by a new class of antibacterial agents. Nature 2010, 466(7309), 935-940; Gomez, L.; Hack, M. D.; Wu, J.; Wiener, J. J.;Venkatesan, H.; Santillan, A., Jr.; Pippel, D. J.; Mani, N.; Morrow, B.J.; Motley, S. T.; Shaw, K. J.; Wolin, R.; Grice, C. A.; Jones, T. K.Novel pyrazole derivatives as potent inhibitors of type IItopoisomerases. Part 1: synthesis and preliminary SAR analysis. Bioorg.Med. Chem. Lett. 2007, 17 (10), 2723-2727; and, Wiener, J. J.; Gomez,L.; Venkatesan, H.; Santillan, A., Jr.; Allison, B. D.; Schwarz, K. L.;Shinde, S.; Tang, L.; Hack, M. D.; Morrow, B. J.; Motley, S. T.;Goldschmidt, R. M.; Shaw, K. J.; Jones, T. K.; Grice, C. A.Tetrahydroindazole inhibitors of bacterial type II topoisomerases. Part2: SAR development and potency against multidrug-resistant strains.Bioorg. Med. Chem. Lett. 2007, 17 (10), 2718-2722) andisothiazoloquinolones (e.g., ACH-702)(see, Kim, H. Y.; Wiles, J. A.;Wang, Q.; Pais, G. C. G.; Lucien, E.; Hashimoto, A.; Nelson, D. M.;Thanassi, J. A.; Podos, S. D.; Deshpande, M.; Pucci, M. J.; Bradbury, B.J. Exploration of the activity of7-pyrrolidino-8-methoxyisothiazoloquinolones againstmethicillin-resistant Staphylococcus aureus (MRSA). J. Med. Chem., 2010,54(9), 3268-3282) have been described as new classes of bacterialtopoisomerase inhibitors. The X-ray crystallographic structure ofGSK299423 bound to DNA gyrase has also been reported (Bax, B. D., etal., 2010).

Structurally, most of the known inhibitors (with the exception of QPT-1,the tetrahydroindazoles, NXL101, GSK299423 and ACH-702) possess aketo-acid functionality, either a carboxylic acid (ciprofloxacin andmoxifloxacin, levofloxacin, the monocyclic and bicyclic 2-pyridone and4-pyridones), hydroxylamine (quinazolinediones and tricyclicisoquinolones), or a hydrazine (quinazolinediones) group, which relateto DNA gyrase and topoisomerase activity and presumably bind to adivalent cation in the activated complex (see, Laponogov, I.; Sohi, M.K.; Veselkov, D. A.; Pan, X. S.; Sawhney, R.; Thompson, A. W.; McAuley,K. E.; Fisher, L. M.; Sanderson, M. R. Structural insight into thequinolone-DNA cleavage complex of type HA topoisomerases. Nat. Struct.Mol. Biol. 2009, 16 (6), 667-669).

Most inhibitors also possess an amine functional group attached to thecore heterocycle, making these compounds zwitterionic in nature.Monocyclic 2-pyridone and 4-pyridone (e.g., Ro-13-5478) inhibitorspossess this amine functionality attached to a phenyl group (see,Tesfaye, B.; Heck, J. V.; Thorsett, E. D. European Patent Application0308022 A2, 1987; Narita, H.; Konishi, Y.; Nitta, J.; Misumi, S.;Nagaki, H.; Kitayama, I.; Nagai, Y.; Watanbe, Y.; Matsubare, N.; Minami,S.; Saikawa, I.; UK Patent Application GB2130580, 1983; and, Narita, H.;Konishi, Y.; Nitta, J.; Misumi, S.; Nagaki, H.; Kitayama, I.; Nagai, Y.;Watanbe, Y.; Matsubare, N.; Minami, S.; Saikawa, I. U.S. Pat. No.4,698,352; 1987).

The zwitterionic nature of these inhibitors relate to the permeation ofthese compounds into the Gram-negative cell using porin channels (see,Nikaido, H.; Thanassi, D. G. Penetration of lipophilic agents withmultiple protonation sites into bacterial cells: tetracyclines andfluoroquinolones as examples. Antimicrob. Agents Chemother. 1993, 37(7), 1393-1399; and, Tieleman, D. P.; Berendsen, H. J. A moleculardynamics study of the pores formed by Escherichia coli OmpF porin in afully hydrated palmitoyloleoylphosphatidylcholine bilayer. Biophys. J.1998, 74 (6), 2786-2801).

Due to increasing resistance of multiple bacteria to marketedantibiotics in hospital as well as in community settings, the discoveryof new and especially novel antibiotics is urgently needed (see,Bonhoeffer, S.; Lipsitch, M.; Levin, B. R. Evaluating treatmentprotocols to prevent antibiotic resistance. Proc. Natl. Acad. Sci. U.S.A1997, 94 (22), 12106-12111; Wang, Y. C.; Lipsitch, M. Upgradingantibiotic use within a class: tradeoff between resistance and treatmentsuccess. Proc. Natl. Acad. Sci. U.S.A 2006, 103 (25), 9655-9660; and,Payne, D. J.; Gwynn, M. N.; Holmes, D. J.; Pompliano, D. L. Drugs forbad bugs: confronting the challenges of antibacterial discovery. Nat.Rev. Drug Discov. 2007, 6 (1), 29-40).

Approximately 70% of bacterial strains causing nosocomial infections areresistant to at least one of the drugs most commonly used to treat suchinfections, and 25% of bacterial pneumonia cases have been shown to beresistant to penicillin (Todar, K. Todar's Online textbook ofBacteriology, htttp://www.textbookofbacteriology.net/). Recently, therehas been a dramatic decrease in the number of new antibiotic approvals,where only two new entities have been approved in the past two years.

There are some antibiotics available that have had success against MRSA(see, Perry, C. M.; Jarvis, B. Linezolid: a review of their use in themanagement of serious Gram-positive infections. Drugs 2001, 61 (4),525-551; Peterson, L. R. A review of tigecycline—the firstglycylcycline. Int. J. Antimicrob. Agents 2008, 32 Suppl 4, S215-S222;Chu, D. T. Recent developments in macrolides and ketolides. Curr. Opin.Microbiol. 1999, 2 (5), 467-474; Kahne, D.; Leimkuhler, C.; Lu, W.;Walsh, C. Glycopeptide and lipoglycopeptide antibiotics. Chem. Rev.2005, 105 (2), 425-448; and, Zhanel, G. G.; Lam, A.; Schweizer, F.;Thomson, K.; Walkty, A.; Rubinstein, E.; Gin, A. S.; Hoban, D. J.;Noreddin, A. M.; Karlowsky, J. A. Ceftobiprole: a review of abroad-spectrum and anti-MRSA cephalosporin. Am. J. Clin. Dermatol. 2008,9 (4), 245-254), but there have been no new clinically approved agentstargeting Gram-negative bacteria.

Quinolones have been shown to be highly effective in the clinic, butwide-scale deployment of these current drugs, partly due to genericusage of the effective second generation quinolones (e.g.,ciprofloxacin), jeopardizes their future long-term utility. Quinoloneresistance is already rising in both hospitals and the community atlarge. Therefore, new drugs targeting MDR Gram-negative pathogens wouldbe expected to help address this important unmet medical need (see,Talbot, G. H.; Bradley, J.; Edwards, J. E., Jr.; Gilbert, D.; Scheid,M.; Bartlett, J. G. Bad bugs need drugs: an update on the developmentpipeline from the Antimicrobial Availability Task Force of theInfectious Diseases Society of America. Clin. Infect. Dis. 2006, 42 (5),657-668; and, Rice, L. B. Unmet medical needs in antibacterial therapy.Biochem. Pharmacol. 2006, 71 (7), 991-995).

As resistance to marketed antibiotics continues to increase, and newantibacterials have not been readily forthcoming from the pharmaceuticalindustry, the availability of new antibiotic and antibacterials agentsis essential to overcome pre-existing and burgeoning resistance. As aneffective monotherapy, novel compounds active against MDR strains of E.coli and A. baumannii pathogens, as well as other bacterial strains ofgreat interest are needed, including those potentially employable asbioterror agents. New compounds that bind differently than existing DNAsynthesis inhibitors and new therapies with combinations ofantibacterial and antibiotic agents having additive or synergisticactivities, including combinations with current quinolone antibiotics,would enable longer clinical lifetimes for proven antibacterial agentsagainst a mechanistically validated target. Accordingly, theavailability of such compounds and therapies would provide a significantcurrent and future human health benefit with a high probability ofsuccess on several fronts for the control of difficult bacterialinfections for a number of years to come.

6-methoxyquinoline based compounds for use as antibacterialtopoisomerase inhibitors possessing Gram-negative activities have beenreported by Glaxo-SmithKline, Johnson & Johnson and Novexel. Achillionand Rib-x Pharmaceuticals have also reported isothiazoloquinolones andquinolone (delafloxacin), respectively, that possess activity againstresistant Gram-positive strains, including MRSA. Other examples in theliterature include AM-1954 (Kyorin), DC-159a and DX-619 (Diaiichi),JNJ-Q2 (Johnson & Johnson), WQ-3813 (Wakunaga). However, all thesecompounds are derived from a quinolone moiety. Pfizer, Astra Zeneca,Achaogen and Targanta further describe quinolone-based compounds thatpossess an expanded spectrum of activity, especially againstGram-positive strains. Recently, the literature from 2005 to 2010 hasbeen surveyed for new quinolone antibiotics (see, Wiles, J. A.;Bradbury, B. J.; Pucci, M. J. New quinolone antibiotics: a survey of theliterature from 2005 to 2010. Expert Opin. Ther. Patents, 2010, 20(10),1295-1319), including the development of compounds by AstraZeneca,Vertex Pharmaceuticals and Pfizer that act on the gyrase B sub-unit ofthe enzyme.

Despite the availability of quinolone based agents, the pre-existing andburgeoning resistance to such agents requires the availability of newantibiotic and antibacterials agents. However, the high conservation ofsequence identity between DNA gyrase and topoisomerase IV enzymescontinues to provide an opportunity for the discovery and development ofnon-quinolone inhibitors possessing a broad spectrum of activity againstthese targets. The present description relates to compounds havingactivity toward wild-type and MDR bacteria. The present description alsorelates to compounds having activity against quinolone-resistantGram-negative strains (including MDR strains) as well as antibacterialactivity to MDR resistant Gram-positive pathogens (including MRSAstrains). The present description also relates to compounds withselectivity between bacterial topoisomerase IV and DNA gyrase enzymeinhibition compared to human topoisomerase II enzyme inhibition. Thepresent description further relates to compounds that may be combinedwith known antibacterial agents to provide additive or synergisticactivity, thus enabling the development of a combination product for thetreatment of Gram-negative (especially MDR strains) and Gram-positiveinfections.

All other documents referred to herein are incorporated by referenceinto the present application as though fully set forth herein.

SUMMARY

The present description relates to a compound of Formula (I):

wherein R₁, R₂, R₃ and R₄ are as defined herein, and forms andcompositions thereof, and also relates to uses of the compound ofFormula (I) and methods of treating or ameliorating a bacterialinfection, or for treating or ameliorating a multi-drug resistant (MDR)bacterial infection.

The present description further relates to a compound of Formula (I)having activity toward wild-type and MDR bacteria. The presentdescription also relates to a compound of Formula (I) having activityagainst quinolone-resistant Gram-negative strains (including MDRstrains) as well as antibacterial activity to MDR resistantGram-positive pathogens (including MRSA strains). The presentdescription also relates to a compound of Formula (I) having selectivitybetween bacterial topoisomerase IV and DNA gyrase enzyme inhibitioncompared to human topoisomerase II enzyme inhibition. The presentdescription further relates to a compound of Formula (I) that may becombined with known antibacterial agents to provide additive orsynergistic activity, thus enabling the development of a combinationproduct for the treatment of Gram-negative (especially MDR strains) andGram-positive infections.

DETAILED DESCRIPTION

The present description relates to a compound of Formula (I):

-   or a form thereof, wherein-   R₁ is phenyl, thienyl, pyrrolyl, pyrazolyl, pyridinyl, pyrimidinyl    or pyrazinyl, each optionally substituted with one, two or three    substituents each selected from R₅ and one additional substituent    selected from R₆;-   R₂ is hydrogen, halogen, cyano, C₁₋₈alkyl, halo-C₁₋₈alkyl,    hydroxyl-C₁₋₈alkyl, formyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl,    C₁₋₈alkoxy, C₂₋₈alkenyl, C₂₋₈alkynl, carboxyl, amino,    C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    C₃₋₁₄cycloalkyl, C₃₋₈cycloalkyl-oxy, aryl or aryl-C₁₋₈alkyl, wherein    each instance of aryl is optionally substituted with one halogen    substituent;-   R₃ is hydrogen, halogen, hydroxyl, C₁₋₈alkyl, C₁₋₈alkoxy, carboxyl,    amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino or C₁₋₈alkyl-SO₂-amino;-   R₄ is hydrogen or C₁₋₈alkyl;-   R₅ is halogen, hydroxyl, oxo, cyano, nitro, C₁₋₈alkyl,    hydroxyl-C₁₋₈alkyl, halo-C₁₋₈alkyl, C₁₋₈alkoxy, halo-C₁₋₈alkoxy,    C₁₋₈alkyl-thio, carboxyl, C₁₋₈alkyl-carbonyl, C₁₋₈alkoxy-carbonyl,    amino-carbonyl, amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino,    C₂₋₈alkenyl-amino, (C₂₋₈alkenyl)₂-amino, C₂₋₈alkynyl-amino,    (C₂₋₈alkynyl)₂-amino, amino-C₁₋₈alkyl, C₁₋₁₀alkyl-amino-C₁₋₈alkyl,    (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₂₋₈alkenyl-amino-C₁₋₈alkyl,    (C₂₋₈alkenyl)₂-amino-C₁₋₈alkyl, C₂₋₈alkynyl-amino-C₁₋₈alkyl,    (C₂₋₈alkynyl)₂-amino-C₁₋₈alkyl, halo-C₁₋₈alkyl-amino,    (halo-C₁₋₈alkyl)₂-amino, halo-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (halo-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl-amino,    (C₁₋₈alkoxy-C₁₋₈alkyl, C₁₋₈alkyl)-amino,    (C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino, C₁₋₈alkoxy-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (C₁₋₈alkoxy-C₁₋₈alkyl, C₁₋₈alkyl)-amino-C₁₋₈alkyl,    (C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, amino-C₁₋₈alkyl-amino,    (amino-C₁₋₈alkyl, C₁₋₈alkyl)amino, C₁₋₈alkyl-amino-C₁₋₈alkyl-amino,    (C₁₋₈alkyl-amino-C₁₋₈alkyl, C₁₋₈alkyl)amino,    (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino, [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    C₁₋₈alkyl]amino, amino-C₁₋₈alkyl-amino-C₁₋₈alkyl, (amino-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (C₁₋₈alkyl-amino-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,    [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₁₋₈alkyl]amino-C₁₋₈alkyl,    hydroxyl-amino, hydroxyl-C₁₋₈alkyl-amino, (hydroxyl-C₁₋₈alkyl,    C₁₋₈alkyl)amino, (hydroxyl-C₁₋₈alkyl)₂-amino,    hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (hydroxyl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl-amino,    (hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, C₁₋₈alkyl)amino,    (hydroxyl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl-amino,    [(hydroxyl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, C₁₋₈alkyl]amino,    (C₁₋₈alkyl-carbonyl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-carbonyl, (C₁₋₈alkyl)₂-amino-carbonyl or    (C₁₋₈alkyl)₂-arnino-carbonyl-C₁₋₈alkyl-amino-C₁₋₈alkyl;-   R₆ is C₃₋₁₄cycloalkyl, C₃₋₁₄cycloalkyl-C₁₋₈alkyl,    C₃₋₁₄cycloalkyl-oxy, C₃₋₁₄cycloalkyl-C₁₋₈alkoxy,    C₃₋₁₄cycloalkyl-amino, C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl,    (C₃₋₁₄cycloalkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (C₃₋₁₄cycloalkyl)₂-amino-C₁₋₈alkyl,    C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (C₃₋₁₄cycloalkyl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (C₃₋₁₄cycloalkyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, aryl, aryl-C₁₋₈alkyl,    aryl-C₁₋₈alkoxy, aryl-amino, (aryl, C₁₋₈alkyl)amino, (aryl)₂-amino,    aryl-amino-C₁₋₈alkyl, (aryl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (aryl)₂-amino-C₁₋₈alkyl, aryl-C₁₋₈alkyl-amino, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,    aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    heteroaryl, heteroaryl-C₁₋₈alkyl, heteroaryl-amino,    heteroaryl-C₁₋₈alkyl-amino, (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino,    (heteroaryl-C₁₋₈alkyl)₂-amino, heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, heterocyclyl,    heterocyclyl-C₁₋₈alkyl, heterocyclyl-oxy, heterocyclyl-C₁₋₈alkoxy,    heterocyclyl-amino, (heterocyclyl, C₁₋₈alkyl)amino,    (heterocyclyl)₂-amino, heterocyclyl-amino-C₁₋₈alkyl, (heterocyclyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (heterocyclyl)₂-amino-C₁₋₈alkyl,    (heterocyclyl, C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl,    heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (heterocyclyl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl,    (heterocyclyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heterocyclyl-oxy-amino,    (heterocyclyl-oxy, C₁₋₈alkyl)amino, (heterocyclyl-oxy)₂-amino,    (heterocyclyl-oxy-C₁₋₈alkyl, C₁₋₈alkyl)amino, heterocyclyl-carbonyl    or heterocyclyl-carbonyl-oxy;-   wherein each instance of heterocyclyl is optionally substituted with    one, two or three substituents each selected from R₇; and,-   wherein each instance of C₃₋₁₄cycloalkyl, aryl and heteroaryl is    optionally substituted with one, two or three substituents each    selected from R₈;-   R₇ is azido, halogen, hydroxyl, oxo, cyano, nitro, C₁₋₈alkyl,    halo-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl,    C₁₋₈alkoxy, halo-C₁₋₈alkoxy, hydroxyl-C₁₋₈alkoxy, carboxyl,    C₁₋₈alkyl-carbonyl, C₁₋₈alkoxy-carbonyl, amino, C₁₋₈alkyl-amino,    (C₁₋₈alkyl)₂-amino, halo-C₁₋₈alkyl-amino, (halo-C₁₋₈alkyl)₂-amino,    halo-C₁₋₈alkyl-amino-C₁₋₈alkyl, (halo-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    amino-C₁₋₈alkyl, C₁₋₈alkyl-amino-C₁₋₈alkyl,    (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    C₁₋₈alkyl]amino-C₁₋₈alkyl C₁₋₈alkyl-thio, amino-carbonyl,    C₁₋₈alkyl-amino-carbonyl, (C₁₋₈alkyl)₂-amino-carbonyl,    C₁₋₈alkyl-carbonyl-amino, (carboxyl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-carbonyl-amino, C₃₋₁₄cycloalkyl,    C₃₋₁₄cycloalkyl-amino, aryl, aryl-C₁₋₈alkyl, aryl-amino, (aryl,    C₁₋₈alkyl)amino, (aryl)₂-amino, aryl-C₁₋₈alkyl-amino,    (aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,    aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    aryl-amino-C₁₋₈alkyl, (aryl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (aryl)₂-amino-C₁₋₈alkyl, aryl-amino-carbonyl, aryl-C₁₋₈alkoxy,    aryl-C₁₋₈alkoxy-carbonyl-amino, heteroaryl, heteroaryl-C₁₋₈alkyl,    heteroaryl-amino, (heteroaryl)₂-amino, heteroaryl-C₁₋₈alkyl-amino,    (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino,    (heteroaryl-C₁₋₈alkyl)₂-amino, heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl,    (heteroaryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heterocyclyl,    heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl or    heterocyclyl-oxy;-   wherein each instance of C₃₋₁₄cycloalkyl is optionally substituted    with one substituent selected from R₉;-   wherein each instance of aryl is optionally substituted with one    substituent selected from R₁₀; and,-   wherein each instance of heterocyclyl and heteroaryl is optionally    substituted with one substituent selected from R₁₁;-   R₈ is azido, halogen, hydroxyl, cyano, nitro, C₁₋₈alkyl,    halo-C₁₋₈alkyl, C₁₋₈alkoxy, C₁₋₈alkoxy-C₁₋₈alkyl, halo-C₁₋₈alkoxy,    carboxyl, C₁₋₈alkoxy-carbonyl, amino, C₁₋₈alkyl-amino,    (C₁₋₈alkyl)₂-amino, C₁₋₈alkyl-thio, aryl, aryl-C₁₋₈alkoxy,    heteroaryl, heterocyclyl, heterocyclyl-C₁₋₈alkyl or    heterocyclyl-oxy;-   R₉ is amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl or    aryl-C₁₋₈alkyl-amino;-   R₁₀ is halogen; and,-   R₁₁ is halogen, hydroxyl, C₁₋₈alkyl, halo-C₁₋₈alkyl, C₁₋₈alkoxy,    C₁₋₈alkoxy-C₁₋₈alkyl, halo-C₁₋₈alkoxy, amino, C₁₋₈alkyl-amino or    (C₁₋₈alkyl)₂-amino.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₁ is thien-2-yl, pyrrol-2-yl,pyrrol-3-yl, 1H-pyrazol-2-yl, 1H-pyrazol-4-yl, pyrazin-2-yl,pyrimidin-5-yl, pyridin-2-yl or pyridin-3-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₂, R₆, R₇ and R₈ is

-   C₃₋₁₄cycloalkyl selected in each instance, when present, from    cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl;-   aryl selected in each instance, when present, from phenyl;-   heteroaryl selected in each instance, when present, from pyrrolyl,    thiazolyl, 1H-1,2,3-triazolyl, 1H-tetrazolyl, 2H-tetrazolyl,    imidazolyl or pyridinyl;-   heterocyclyl selected in each instance, when present, from    azetidinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl,    piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,    2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl,    1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,    tetrahydro-2H-pyranyl, indolinyl, 2,3-dihydrobenzo[d]oxazolyl,    3,4-dihydro-2H-benzo[b][1,4]oxazinyl,    3,4-dihydroisoquinolin-(1H)-yl, 1,2,3,4-tetrahydroisoquinolinyl,    1,2,3,4-tetrahydroquinoxalinyl,    hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,    3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl,    (cis)-octahydrocyclopenta[c]pyrrolyl,    hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,    5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    octahydro-6H-pyrrolo[3,4-b]pyridinyl,    2,3,4,9-tetrahydro-1H-carbazolyl,    1,2,3,4-tetrahydropyrazino[1,2-a]indolyl,    2,3-dihydro-1H-pyrrolo[1,2-a]indolyl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    (3aR,7aS)-octahydro-2H-isoindolyl,    (3aR,4R,7aS)-octahydro-2H-isoindolyl,    (3aR,4S,7aS)-octahydro-2H-isoindolyl,    2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl,    3-azabicyclo[3.1.0]hexanyl, (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,    (cis,cis)-3-azabicyclo[3.1.0]hexanyl,    3,6-diazabicyclo[3.1.0]hexanyl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,    2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,    2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,    2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl or    2,8-diazaspiro[4.5]decanyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆, R₇ and R₈ is

-   heteroaryl selected in each instance, when present, from    pyrrol-1-yl, thiazol-2-yl, 1H-1,2,3-triazol-1-yl, 1H-tetrazol-5-yl,    2H-tetrazol-2-yl, imidazol-1-yl, pyridin-2-yl, pyridin-3-yl or    pyridin-4-yl;-   heterocyclyl selected in each instance, when present, from    azetidin-1-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl,    tetrahydrofuran-2-yl, piperidin-1-yl, piperidin-2-yl,    piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, piperazin-2-yl,    morpholin-4-yl, 1,4-diazepan-1-yl, 1,3-dioxolan-2-yl,    2,5-dihydro-1H-pyrrol-1-yl, dihydro-1H-imidazol-2-yl,    1,4,5,6-tetrahydropyrimidin-2-yl, 1,2,3,6-tetrahydropyridin-4-yl,    tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl,    3,4-dihydroisoquinolin-2(1H)-yl, 1,2,3,4-tetrahydroisoquinolin-1-yl,    hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl,    (cis)-octahydrocyclopenta[c]pyrrol-4-yl,    hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl,    5H-pyrrolo[3,4-b]pyridin-6(7H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl,    hexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl,    (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl,    octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    1,3-dihydro-2H-isoindol-2-yl, octahydro-2H-isoindol-2-yl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl,    (3aR,4R,7aS)-1H-isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl,    (3aR,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl,    2,5-diazabicyclo[2.2.1]heptan-2-yl,    2-azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl,    (cis,cis)-3-azabicyclo[3.1.0]hexan-3-yl,    3,6-diazabicyclo[3.1.0]hexan-3-yl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptan-3-yl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptan-3-yl,    5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl,    2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl,    2,7-diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl,    2-azaspiro[4.5]decan-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆, R₇ and R₈ is

-   heteroaryl selected in each instance, when present, from pyridinyl;-   heterocyclyl selected in each instance, when present, from    azetidinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl,    piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,    dihydro-1H-imidazolyl, 1,4,5,6-tetrahydropyrimidinyl,    1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl,    3,4-dihydroisoquinolin-(1H)-yl, 1,2,3,4-tetrahydroisoquinolinyl,    5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    2,5-diazabicyclo[2.2.1]heptanyl or    (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆, R₇ and R₈ is

-   heteroaryl selected in each instance, when present, from    pyridin-2-yl, pyridin-3-yl or pyridin-4-yl;-   heterocyclyl selected in each instance, when present, from    azetidin-1-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl,    tetrahydrofuran-2-yl, piperidin-1-yl, piperidin-2-yl,    piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, piperazin-2-yl,    morpholin-4-yl, 1,4-diazepan-1-yl, 1,3-dioxolan-2-yl,    dihydro-1H-imidazol-2-yl, 1,4,5,6-tetrahydropyrimidin-2-yl,    1,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl,    tetrahydro-2H-pyran-4-yl, 3,4-dihydroisoquinolin-2(1H)-yl,    1,2,3,4-tetrahydroisoquinolin-1-yl,    5H-pyrrolo[3,4-b]pyridin-6(7H)-yl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,4R,7aS)-1H-isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl,    2,5-diazabicyclo[2.2.1]heptan-2-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl or    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆, R₇ and R₈ is

-   heteroaryl selected in each instance, when present, from pyrrolyl,    imidazolyl, 1H-tetrazolyl or 2H-tetrazolyl;-   heterocyclyl selected in each instance, when present, from    azetidinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl,    piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,    2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl,    1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,    tetrahydro-2H-pyranyl, 3,4-dihydroisoquinolin-(1H)-yl,    1,2,3,4-tetrahydroisoquinolinyl,    hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,    (cis)-octahydrocyclopenta[c]pyrrolyl,    hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,    5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    octahydro-6H-pyrrolo[3,4-b]pyridinyl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    (3aR,7aS)-octahydro-2H-isoindolyl,    (3aR,4R,7aS)-octahydro-2H-isoindolyl,    (3aR,4S,7aS)-octahydro-2H-isoindolyl,    2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl,    3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.0]hexanyl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,    2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,    2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,    2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl or    2,8-diazaspiro[4.5]decanyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆, R₇ and R₈ is

-   heteroaryl selected in each instance, when present, from    1H-tetrazol-5-yl, imidazol-1-yl, pyrrol-1-yl or 2H-tetrazol-2-yl;-   heterocyclyl selected in each instance, when present, from    azetidin-1-yl, pyrrolidin-1-yl, tetrahydrofuran-2-yl,    piperidin-1-yl, piperazin-1-yl, morpholin-4-yl,    2,5-dihydro-1H-pyrrol-1-yl,    hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    1,3-dihydro-2H-isoindol-2-yl, octahydro-2H-isoindol-2-yl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl,    (3aR,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl,    2,5-diazabicyclo[2.2.1]heptan-2-yl,    2-azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hexan-3-yl,    3,6-diazabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptan-3-yl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptan-3-yl,    5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl,    2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl,    2,7-diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl,    2-azaspiro[4.5]decan-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein

-   R₂ is hydrogen, cyano, C₁₋₈alkyl, halo-C₁₋₈alkyl,    hydroxyl-C₁₋₈alkyl, formyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl,    C₂₋₈alkenyl, C₂₋₈alkynyl, carboxyl, C₃₋₁₄cycloalkyl, aryl or    aryl-C₁₋₈alkyl, wherein each instance of aryl is optionally    substituted with one halogen substituent;-   R₃ is hydrogen, halogen, hydroxyl, C₁₋₈alkoxy, carboxyl, amino or    C₁₋₈alkyl-SO₂-amino;-   R₄ is hydrogen or C₁₋₈alkyl;-   R₅ is halogen, oxo, cyano, C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl,    C₁₋₈alkoxy, carboxyl, amino-carbonyl, amino, C₁₋₈alkyl-amino,    (C₁₋₈alkyl)₂-amino, (C₂₋₈alkenyl)₂-amino, amino-C₁₋₈alkyl,    C₁₋₁₀alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    C₂₋₈alkenyl-amino-C₁₋₈alkyl, C₂₋₈alkynyl-amino-C₁₋₈alkyl,    halo-C₁₋₈alkyl-amino, halo-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (hydroxyl-C₁₋₈alkyl, C₁₋₈alkyl)amino, (C₁₋₈alkoxy-C₁₋₈alkyl,    C₁₋₈alkyl)-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino,    [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₁₋₈alkyl]amino,    amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,    [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₁₋₈alkyl]amino-C₁₋₈alkyl,    (C₁₋₈alkyl-carbonyl, C₁₋₈alkyl)amino-C₁₋₈alkyl or    (C₁₋₈alkyl)₂-amino-carbonyl-C₁₋₈alkyl-amino-C₁₋₈alkyl;-   R₆ is C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl, (C₃₋₁₄cycloalkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl,    C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, aryl, aryl-C₁₋₈alkoxy,    aryl-amino, (aryl, C₁₋₈alkyl)amino, aryl-amino-C₁₋₈alkyl,    aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    heteroaryl, heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,    (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, heterocyclyl,    heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl, (heterocyclyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (heterocyclyl,    C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl,    heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl or    (heterocyclyl-oxy-C₁₋₈alkyl, C₁₋₈alkyl)amino;-   wherein each instance of heterocyclyl is optionally substituted with    one, two or three substituents each selected from R₇; and,-   wherein each instance of heteroaryl is optionally substituted with    one, two or three substituents each selected from R₈;-   R₇ is azido, halogen, hydroxyl, oxo, cyano, C₁₋₈alkyl,    halo-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl,    C₁₋₈alkoxy, carboxyl, C₁₋₈alkyl-carbo nyl, C₁₋₈alkoxy-carbonyl,    amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,    C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    [(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    C₁₋₈alkyl]amino-C₁₋₈alkyl(C₁₋₈alkyl)₂-amino-carbonyl,    C₁₋₈alkyl-carbonyl-amino, (carboxyl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-carbonyl-amino, C₃₋₁₄cycloalkyl,    C₃₋₁₄cycloalkyl-amino, aryl, aryl-C₁₋₈alkyl, aryl-amino, (aryl,    C₁₋₈alkyl)amino, aryl-C₁₋₈alkyl-amino, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,    aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl,    C₁₋₈alkyl)amino-C₁₋₈alkyl, (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,    aryl-amino-C₁₋₈alkyl, aryl-C₁₋₈alkoxy,    aryl-C₁₋₈alkoxy-carbonyl-amino, heteroaryl,    heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, heterocyclyl,    heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl or    heterocyclyl-oxy;-   wherein each instance of C₃₋₁₄cycloalkyl is optionally substituted    with one substituent selected from R₉;-   wherein each instance of aryl is optionally substituted with one    substituent selected from R₁₀; and,-   wherein each instance of heterocyclyl and heteroaryl is optionally    substituted with one substituent selected from R₁₁;-   R₈ is C₁₋₈alkyl;-   R₉ is amino, (C₁₋₈alkyl)₂-amino or aryl-C₁₋₈alkyl-amino;-   R₁₀ is halogen; and,-   R₁₁ is C₁₋₈alkyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein

-   R₂ is C₁₋₈alkyl selected from methyl, ethyl, propyl or isopropyl;    hydroxyl-C₁₋₈alkyl selected from hydroxyl-methyl, hydroxyl-ethyl or    hydroxyl-propyl; formyl-C₁₋₈alkyl selected from formylmethyl,    formylethyl or formylpropyl; C₃₋₁₄cycloalkyl selected from    cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; aryl selected    from phenyl; and, aryl-C₁₋₈alkyl selected from benzyl;-   R₃ is C₁₋₈alkoxy selected from methoxy, ethoxy, propoxy or    isopropoxy; or, C₁₋₈alkyl-SO₂-amino selected from methyl-SO₂-amino,    ethyl-SO₂-amino, propyl-SO₂-amino or isopropyl-SO₂-amino; and,-   R₄ is C₁₋₈alkyl selected from methyl, ethyl, propyl or isopropyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein

-   R₂ is C₃₋₁₄cycloalkyl selected from cyclopropyl or cyclobutyl and    aryl selected from phenyl; and-   R₃ is C₁₋₈alkoxy selected from methoxy, ethoxy, propoxy or    isopropoxy.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₂ is

-   C₁₋₈alkyl selected from methyl, ethyl, propyl or isopropyl;-   C₃₋₁₄cycloalkyl selected from cyclopropyl, cyclopentyl or    cyclohexyl; or,-   aryl-C₁₋₈alkyl selected from benzyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₂ is C₃₋₁₄cycloalkyl selected fromcyclopropyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₃ is C₁₋₈alkoxy selected from methoxy orethoxy.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₄ is C₁₋₈alkyl selected from methyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆ is

-   C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl, wherein C₃₋₁₄cycloalkyl is selected    from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;-   (C₃₋₁₄cycloalkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein C₃₋₁₄cycloalkyl    is selected from cyclopropyl, cyclobutyl or cyclopentyl;-   C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein C₃₋₁₄cycloalkyl    is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or    cycloheptyl; aryl, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkoxy, wherein aryl is selected from phenyl;-   aryl-amino, wherein aryl is selected from phenyl;-   (aryl, C₁₋₈alkyl)amino, wherein aryl is selected from phenyl;-   aryl-amino-C₁₋₈alkyl, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein aryl is selected from    phenyl;-   (aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein aryl is selected    from phenyl;-   (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, wherein aryl is selected from    phenyl;-   heteroaryl, wherein heteroaryl is selected from pyrrolyl, thiazolyl,    1H-1,2,3-triazolyl, 1H-tetrazolyl, 2H-tetrazolyl, imidazolyl or    pyridinyl;-   heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heteroaryl is selected    from pyridin-2-yl, pyridin-3-yl or pyridin-4-yl;-   (heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein heteroaryl    is selected from pyridin-3-yl or pyridin-4-yl;-   heterocyclyl, wherein heterocyclyl is selected from azetidinyl,    pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl,    morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,    2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl,    1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,    tetrahydro-2H-pyranyl, 3,4-dihydroisoquinolin-(1H)-yl,    1,2,3,4-tetrahydroisoquinolinyl,    hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,    (cis)-octahydrocyclopenta[c]pyrrolyl,    hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,    5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    octahydro-6H-pyrrolo[3,4-b]pyridinyl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    (3aR,7aS)-octahydro-2H-isoindolyl,    (3aR,4R,7aS)-octahydro-2H-isoindolyl,    (3aR,4S,7aS)-octahydro-2H-isoindolyl,    2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl,    3-azabicyclo[3.1.0]hexanyl, (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,    (cis,cis)-3-azabicyclo[3.1.0]hexanyl,    3,6-diazabicyclo[3.1.0]hexanyl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,    2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,    2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,    2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl or    2,8-diazaspiro[4.5]decanyl;-   heterocyclyl-C₁₋₈alkyl, wherein heterocyclyl is selected from    azetidinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl,    piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,    2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl,    1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,    tetrahydro-2H-pyranyl, 3,4-dihydroisoquinolin-(1H)-yl,    1,2,3,4-tetrahydroisoquinolinyl,    hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,    (cis)-octahydrocyclopenta[c]pyrrolyl,    hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,    5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,    octahydro-6H-pyrrolo[3,4-b]pyridinyl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    (3aR,7aS)-octahydro-2H-isoindolyl,    (3aR,4R,7aS)-octahydro-2H-isoindolyl,    (3aR,4S,7aS)-octahydro-2H-isoindolyl,    2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl,    3-azabicyclo[3.1.0]hexanyl, (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,    (cis,cis)-3-azabicyclo[3.1.0]hexanyl,    3,6-diazabicyclo[3.1.0]hexanyl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,    2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,    2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,    2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl or    2,8-diazaspiro[4.5]decanyl;-   heterocyclyl-amino-C₁₋₈alkyl, wherein heterocyclyl is selected from    azetidin-1-yl or piperidin-4-yl;-   (heterocyclyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein heterocyclyl is    selected from piperidin-3-yl or piperidin-4-yl;-   (heterocyclyl, C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein    heterocyclyl is selected from piperidin-3-yl or piperidin-4-yl;-   heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heterocyclyl is    selected from pyrrolidin-2-yl, piperidin-2-yl, piperidin-3-yl,    piperidin-4-yl or tetrahydro-2H-pyran-4-yl; and-   (heterocyclyl-oxy-C₁₋₈alkyl, C₁₋₈alkyl)amino selected from    tetrahydro-2H-pyran-2-yl-oxy-C₁₋₈alkyl, C₁₋₈alkyl)amino.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆ is

-   heteroaryl, wherein heteroaryl is selected from 1H-tetrazolyl,    imidazolyl, pyrrolyl or 2H-tetrazolyl; and,-   heterocyclyl, wherein heterocyclyl is selected from azetidinyl,    pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl,    morpholinyl, 2,5-dihydro-1H-pyrrolyl, 1,2,3,6-tetrahydropyridinyl,    hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,    octahydro-6H-pyrrolo[3,4-b]pyridinyl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,    (3aR,7aS)-octahydro-2H-isoindolyl,    (3aR,4R,7aS)-octahydro-2H-isoindolyl,    (3aR,4S,7aS)-octahydro-2H-isoindolyl,    2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl,    3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.0]hexanyl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,    2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,    2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,    2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl or    2,8-diazaspiro[4.5]decanyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆ is

-   heteroaryl, wherein heteroaryl is selected from 1H-tetrazol-5-yl,    imidazol-1-yl, pyrrol-1-yl or 2H-tetrazol-2-yl; and, heterocyclyl,    wherein heterocyclyl is selected from azetidin-1-yl,    pyrrolidin-1-yl,-   tetrahydrofuran-2-yl, piperidin-1-yl, piperazin-1-yl,    morpholin-4-yl, 2,5-dihydro-1H-pyrrol-1-yl,    1,2,3,6-tetrahydropyridin-4-yl,    hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl,    (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl,    (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,    (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl,    5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl,    (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    1,3-dihydro-2H-isoindol-2-yl, octahydro-2H-isoindol-2-yl,    (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl,    (3aR,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl,    (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl,    2,5-diazabicyclo[2.2.1]heptan-2-yl,    2-azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hexan-3-yl,    3,6-diazabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl,    (1S,5R,6R)-3-azabicyclo[3.2.0]heptan-3-yl,    (1S,5R,6S)-3-azabicyclo[3.2.0]heptan-3-yl,    5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl,    2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl,    2,7-diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl,    2-azaspiro[4.5]decan-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆ is

-   heteroaryl, wherein heteroaryl is selected from pyridinyl; and,-   heterocyclyl, wherein heterocyclyl is selected from azetidinyl,    pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl,    1,3-dioxolanyl, dihydro-1H-imidazolyl,    1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,    tetrahydro-2H-pyranyl, 3,4-dihydroisoquinolin-(1H)-yl,    1,2,3,4-tetrahydroisoquinolinyl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,    (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,    2,5-diazabicyclo[2.2.1]heptanyl or    (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₆ is

-   heteroaryl selected in each instance, when present, from    pyridin-2-yl, pyridin-3-yl or pyridin-4-yl;-   heterocyclyl selected in each instance, when present, from    azetidin-1-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl,    tetrahydrofuran-2-yl, piperidin-1-yl, piperidin-2-yl,    piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, piperazin-2-yl,    morpholin-4-yl, 1,4-diazepan-1-yl, 1,3-dioxolan-2-yl,    dihydro-1H-imidazol-2-yl, 1,4,5,6-tetrahydropyrimidin-2-yl,    1,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl,    tetrahydro-2H-pyran-4-yl, 3,4-dihydroisoquinolin-2(1H)-yl,    1,2,3,4-tetrahydroisoquinolin-1-yl,    5H-pyrrolo[3,4-b]pyridin-6(7H)-yl,    tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl,    (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,    (3aR,4R,7aS)-1H-isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl,    2,5-diazabicyclo[2.2.1]heptan-2-yl,    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl or    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₇ is

-   C₃₋₁₄cycloalkyl, wherein C₃₋₁₄cycloalkyl is selected from    cyclopropyl or cyclobutyl;-   C₃₋₁₄cycloalkyl-amino, wherein C₃₋₁₄cycloalkyl is selected from    cyclopropyl;-   aryl, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkyl, wherein aryl is selected from phenyl;-   aryl-amino, wherein aryl is selected from phenyl;-   (aryl, C₁₋₈alkyl)amino, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkyl-amino, wherein aryl is selected from phenyl;-   (aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino, wherein aryl is selected from    phenyl;-   (aryl-C₁₋₈alkyl-amino, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein aryl is selected from    phenyl;-   (aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein aryl is selected    from phenyl;-   (aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein aryl is selected from    phenyl;-   aryl-C₁₋₈alkoxy, wherein aryl is selected from phenyl;-   aryl-C₁₋₈alkoxy-carbonyl-amino, wherein aryl is selected from    phenyl;-   heteroaryl, wherein heteroaryl is selected from pyridin-2-yl,    pyridin-4-yl, thiazol-2-yl or 1H-1,2,3-triazol-1-yl;-   heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heteroaryl is selected    from pyridin-2-yl, pyridin-3-yl or pyridin-4-yl;-   heterocyclyl, wherein heterocyclyl is selected from pyrrolidin-1-yl    or morpholin-4-yl;-   heterocyclyl-C₁₋₈alkyl, wherein heterocyclyl is selected from    pyrrolidin-1-yl; and,-   heterocyclyl-oxy, wherein heterocyclyl is selected from    tetrahydro-2H-pyran-2-yloxy.

One embodiment of the present description includes a compound of Formula(I) or a form thereof, wherein R₇ is

-   aryl, wherein aryl is selected from phenyl;-   (aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino, wherein aryl is selected from    phenyl;-   (aryl-C₁₋₈alkyl-amino, wherein aryl is selected from phenyl;-   aryl-amino-C₁₋₈alkyl, wherein aryl is selected from phenyl;-   heteroaryl, wherein heteroaryl is selected from pyridin-2-yl or    pyridin-4-yl;-   heterocyclyl, wherein heterocyclyl is selected from piperidin-1-yl;    and,-   heterocyclyl-amino-C₁₋₈alkyl, wherein heterocyclyl is selected from    (1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl.

The present description also relates to a compound of Formula (Ia):

or a form thereof, wherein R₂, R₅ and R₆ are as previously definedherein.

In another embodiment of the present description, a compound or a formthereof is selected from:

wherein the form of the compound is selected from a free acid, freebase, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph or tautomer formthereof, and wherein the form is isolated for use.

In another embodiment of the present description, a compound or a formthereof is selected from:

Cpd Name 15-benzyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 25-benzyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 36-(4-aminophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 46-[4-(dimethylamino)phenyl]-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 56-[4-(dimethylamino)phenyl]-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 65-cyclohexyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 75-cyclohexyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 86-[4-(dimethylamino)phenyl]-2-oxo-5-propyl-1,2-dihydropyridine-3-carboxylicacid 96-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridine-3-carboxylic acid 106-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxylic acid 116-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3,5-dicarboxylicacid 125-cyclopropyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 135-cyclopropyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 145-cyano-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 15 6-(4-cyanophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 165-ethyl-6-(4-{methyl[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 175-ethyl-6-{4-[(2-hydroxyethyl)(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 185-ethyl-4-hydroxy-6-{4-[(2-hydroxyethyl)(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 196-[2-(dimethylamino)pyrimidin-5-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 206-[2-(dimethylamino)pyrimidin-5-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 214-hydroxy-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 235-ethyl-2-oxo-6-[4-(1H-tetrazol-5-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 245-ethyl-6-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid255-ethyl-4-hydroxy-6-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 265-ethyl-6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid27 5-ethyl-6-(4-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 285-ethyl-4-hydroxy-6-(4-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 295-ethyl-4-hydroxy-2-oxo-6-[2-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 305-ethyl-6-(2-fluoro-4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 315-ethyl-2-oxo-6-[2-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 325-ethyl-4-hydroxy-6-(4-methoxy-2-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 335-ethyl-6-(4-methoxy-2-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 346-(2,4-dimethoxyphenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 355-ethyl-6-[4-methoxy-2-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 366-(2,4-dimethoxyphenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 375-ethyl-6-[2-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 385-ethyl-6-[2-fluoro-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 395-ethyl-4-hydroxy-6-[2-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 406-[2-(dimethylamino)-4-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 415-ethyl-4-hydroxy-2-oxo-6-(2,4,6-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid 425-ethyl-4-hydroxy-2-oxo-6-(2,3,4-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid 435-ethyl-6-[2-fluoro-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 445-ethyl-6-[2-fluoro-4-(piperidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 455-ethyl-4-hydroxy-6-[2-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 465-ethyl-2-oxo-6-[2-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 475-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 485-ethyl-4-hydroxy-6-[4-methoxy-2-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 495-ethyl-4-hydroxy-6-[2-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 505-ethyl-6-[2-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 515-ethyl-4-hydroxy-6-[2-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 525-ethyl-6-[2-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 536-[4-(dimethylamino)-2-fluorophenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 546-[2-(dimethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 556-[4-(dimethylamino)-2-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 566-[4-(dimethylamino)-2-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 576-[4-(dimethylamino)-2-methylphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 586-[2-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 595-ethyl-6-[2-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 606-[2-(dimethylamino)-4-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 616-[4-(dimethylamino)-2-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 626-[4-(dimethylamino)-2-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 636-[4-(dimethylamino)-3-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 646-[4-(dimethylamino)-3-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 656-[4-(dimethylamino)-3-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 665-ethyl-6-[3-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 675-ethyl-4-hydroxy-6-[3-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 685-ethyl-6-[3-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 695-ethyl-4-hydroxy-6-[3-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 705-ethyl-6-[3-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 715-ethyl-4-hydroxy-6-[3-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 725-ethyl-6-[3-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 735-ethyl-4-hydroxy-6-[3-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 745-ethyl-6-(4-fluorophenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 75 5-ethyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carboxylic acid 766-(4-chlorophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid776-(4-chlorophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 78 6-(4-bromophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 796-(4-bromophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 80 5-ethyl-6-(4-iodophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 815-ethyl-4-hydroxy-6-(4-iodophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 825-ethyl-4-hydroxy-6-{4-[(3-iodopropyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 836-[4-(azetidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 845-ethyl-6-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 855-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 866-[6-(dimethylamino)pyridin-3-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 876-[6-(dimethylamino)pyridin-3-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 886-[4-(dimethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 896-[3-fluoro-4-(morpholin-4-yl)phenyl]-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 906-[4-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 916-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]-3-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 936-[4-(dimethylamino)-3-fluorophenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 946-[4-(dimethylamino)-3-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 956-[4-(dimethylamino)phenyl]-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylicacid 966-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylic acid 976-[4-(diethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 986-[4-(diethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 995-ethyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1005-ethyl-4-hydroxy-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 1015-ethyl-2-oxo-6-[4-(1H-pyrrol-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1026-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1046-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1065-ethyl-6-[4-(1H-imidazol-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1075-ethyl-4-hydroxy-6-[4-(1H-imidazol-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1085-ethyl-2-oxo-6-[4-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1095-ethyl-4-hydroxy-2-oxo-6-[4-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1105-ethyl-6-[4-(morpholin-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1116-[4-(azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1125-ethyl-4-hydroxy-6-(5-morpholinopyridin-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1135-ethyl-4-hydroxy-2-oxo-6-[5-(piperazin-1-yl)pyridin-2-yl]-1,2-dihydropyridine-3-carboxylic acid 1145-ethyl-2-oxo-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1155-ethyl-4-hydroxy-2-oxo-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 1165-ethyl-6-[4-(2-methyl-5-oxopyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1175-ethyl-6-{4-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1185-ethyl-2-oxo-6-[4-(3-oxo-2-azaspiro[4.5]dec-2-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 1195-ethyl-2-oxo-6-[4-(3-oxo-2-azabicyclo[2.2.1]hept-5-en-2-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 1205-ethyl-2-oxo-6-{4-[3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 1215-ethyl-6-[4-(3-hydroxyazetidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1225-ethyl-6-{4-[(3R)-3-hydroxypiperidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1235-ethyl-6-[4-(3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1245-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1255-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypiperidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1265-ethyl-4-hydroxy-6-[4-(3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 127 methyl6-{4-[3-(benzyloxy)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate 1286-{4-[3-(benzyloxy)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1296-[4-(3-azidopyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1306-{4-[(3S)-3-azidopyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1376-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1395-ethyl-6-[4-(2-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1415-ethyl-2-oxo-6-{4-[(2R)-2-(trifluoromethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 1425-ethyl-2-oxo-6-{4-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 1446-[4-(3,3-difluoropyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1455-ethyl-2-oxo-6-[4-(2-phenylpyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1465-ethyl-6-{4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1475-ethyl-6-{4-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1486-{4-[(2S,5S)-2,5-bis(methoxymethyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1496-{4-[3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1525-ethyl-6-[4-(3-fluoropyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1535-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1545-ethyl-6-{4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1555-ethyl-2-oxo-6-[4-(phenylamino)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1565-ethyl-2-oxo-6-{4-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 1576-{4-[(2S)-2-carboxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1585-ethyl-6-{4-[methyl(phenyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1596-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1605-ethyl-6-{4-[ethyl(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1616-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1626-[4-(1,3-dihydro-2H-isoindol-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1635-isopropyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1645-cyclopropyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid 1656-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylic acid 1676-[4-(3-{[(carboxymethyl)(methyl)carbamoyl]amino}azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1685-ethyl-6-{4-[3-(5-methyl-2H-tetrazol-2-yl)azetidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1706-[4-(3-aminoazetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1716-[4-(3-{[(benzyloxy)carbonyl]amino}azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1736-{4-[3-(cyclopropylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1756-[4-(1,3′-bipyrrolidin-1′-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 1776-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1786-{4-[(1R,5S,6s)-6-(benzylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 1915-ethyl-2-oxo-6-{4-[3-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 1926-[4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2096-[4-(3,6-diazabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2116-{4-[(1S,5R,6R)-6-amino-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2166-{4-[(3S,4R)-3-(aminomethyl)-4-methylpyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2196-[4-(3a-cyanooctahydro-2H-isoindol-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2216-{4-[3-(dimethylamino)pyrrolidin-1-yl]-2-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2225-ethyl-6-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 2236-{4-[4-(dimethylamino)piperidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2245-ethyl-6-[4-(4-methoxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid 2255-ethyl-6-{2-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2265-ethyl-2-oxo-6-{4-[3-(pyridin-4-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 2275-ethyl-2-oxo-6-{4-[3-(pyridin-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 2286-[4-(4-aminopiperidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 2305-ethyl-2-oxo-6-{4-[3-(1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 2325-ethyl-6-[4-(3-ethyl-3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2335-ethyl-6-[4-(3-hydroxy-3-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2346-[4-(3-{[(2-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2356-{4-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2366-[4-(3-{[(3-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2376-[4-(3-{[(4-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2385-ethyl-6-[4-(3-{[(3-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2395-ethyl-6-[4-(3-{[(4-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2405-ethyl-6-[4-(3-{[(2-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2415-ethyl-2-oxo-6-[4-(3-{[(pyridin-3-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 2425-ethyl-2-oxo-6-[4-(3-{[(pyridin-4-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 2435-ethyl-2-oxo-6-[4-(3-{[(pyridin-2-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid 2476-(4-{3-[1-(dimethylamino)cyclopropyl]pyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2486-{4-[(3aR,5r,6aS)-5-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2496-(4-{(3S,4R)-3-[(dibenzylamino)methyl]-4-methylpyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2506-{4-[(3aR,5r,6aS)-5-(benzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2516-{4-[(3aR,5r,6aS)-5-(dibenzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2536-{4-[1-(tert-butoxycarbonyl)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2556-[4-(3-{[benzyl(methyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2805-ethyl-4-hydroxy-6-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2816-{4-[4-(benzyloxy)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2825-ethyl-4-hydroxy-6-[4-(4-methoxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2836-{4-[4-(dibenzylamino)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2846-[4-(4-aminopiperidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2856-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2865-ethyl-4-hydroxy-2-oxo-6-{4-[3-(pyridin-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 2875-ethyl-4-hydroxy-2-oxo-6-{4-[3-(1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid 2885-ethyl-6-[4-(3-ethyl-3-hydroxypyrrolidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2895-ethyl-4-hydroxy-6-[4-(3-hydroxy-3-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2906-{4-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2916-{4-[3-(dimethylamino)pyrrolidin-1-yl]-2-fluorophenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2925-ethyl-6-{2-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2935-ethyl-6-{2-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2946-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2986-[4-(dimethylamino)phenyl]-5-ethyl-4-methoxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 2996-{4-[di(prop-2-en-1-yl)amino]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3006-{4-[di(prop-2-en-1-yl)amino]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3016-[4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3026-[4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3036-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3046-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3056-[5-(dimethylamino)thiophen-2-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3066-[5-(dimethylamino)thiophen-2-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3075-ethyl-4-hydroxy-2-oxo-6-[5-(pyrrolidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylic acid 3085-ethyl-2-oxo-6-[5-(piperidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylicacid 3095-ethyl-4-hydroxy-2-oxo-6-[5-(piperidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylic acid 3106-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid3116-(4-tert-butoxyphenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3126-(5-(dimethylamino)pyrazin-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3135-ethyl-4-hydroxy-2-oxo-6-(5-(pyrrolidin-1-yl)pyrazin-2-yl)-1,2-dihydropyridine-3-carboxylic acid 3146-(5-(3-(dimethylamino)pyrrolidin-1-yl)pyrazin-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3154-hydroxy-5-methyl-2-oxo-6-(5-(pyrrolidin-1-yl)pyridin-2-yl)-1,2-dihydropyridine-3-carboxylic acid 3166-(5-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-2-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3176-(5-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)pyridin-2-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3186-(4-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-2-methylphenyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3195-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3206-(4-(2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3216-(4-(2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3225-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3236-(4-(2,5-diazaspiro[3.4]octan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3246-(4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3255-ethyl-6-(4-(ethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3265-ethyl-4-hydroxy-6-(4-(methylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3276-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylic acid 3286-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3295-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 330(E)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylic acid 3316-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3326-(4-(dimethylamino)phenyl)-4-hydroxy-5-(methoxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3336-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylic acid 3345-ethyl-4-hydroxy-6-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3356-(6-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3365-ethyl-4-hydroxy-2-oxo-6-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1,2-dihydropyridine-3-carboxylic acid 3376-(6-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3385-ethyl-4-hydroxy-6-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3395-ethyl-6-(4-(1-ethylpiperidin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3405-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylic acid 3415-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3425-ethyl-4-hydroxy-6-(4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3436-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3445-ethyl-6-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3455-ethyl-4-hydroxy-6-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3465-ethyl-6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid 3475-ethyl-4-hydroxy-6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3485-ethyl-6-(1-methyl-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3495-ethyl-6-(1-methyl-5-(piperidin-1-ylmethyl)-1H-pyrrol-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3505-ethyl-6-(1-methyl-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3516-(5-((dimethylamino)methyl)-1-methyl-1H-pyrrol-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid 3525-ethyl-6-(1-methyl-5-(piperidin-1-ylmethyl)-1H-pyrrol-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid,and 3536-(5-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-1-methyl-1H-pyrrol-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid;wherein the form of the compound is selected from a free acid, freebase, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph or tautomer formthereof.

In another embodiment, the compound or a form thereof is isolated foruse.

In another embodiment, wherein the compound or a form thereof isselected from:

Cpd Name 225-(aminomethyl)-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride 925-ethyl-6-[3-fluoro-4-(piperazin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate 1035-ethyl-2-oxo-6-[4-(piperazin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate 1055-ethyl-4-hydroxy-2-oxo-6-[4-(piperazin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1316-[4-(3-aminopyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1326-{4-[(3S)-3-aminopyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1336-{4-[(3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1346-{4-[(3R,4R)-3-amino-4-methoxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1356-{4-[(3R,4S)-3-amino-4-methoxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1366-{4-[(3R,4S)-3-amino-4-hydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1386-[4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1405-ethyl-6-{4-[3-(morpholin-4-yl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1435-ethyl-2-oxo-6-{4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1506-{4-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1516-{4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1666-[4-(3-amino-3-methylpyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1696-[4-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1726-{4-[3-(diethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1746-{4-[3-(benzylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1766-{4-[(1R,5S,6s)-6-(dibenzylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1795-ethyl-6-[4-(hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1806-[4-(4-benzylhexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1816-(4-{3-[(dibenzylamino)methyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1826-(4-{3-[(benzylamino)methyl]pyrrolidin-1-yl} phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1836-[4-(3-{[benzyl(methyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1845-ethyl-6-(4-{3-[(methylamino)methyl]pyrrolidin-1-yl} phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1856-(4-{3-[(dimethylamino)methyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1865-ethyl-6-{4-[(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1875-ethyl-6-{4-[(3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1886-{4-[3-(aminomethyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1896-{4-[(3aR,6aR)-1-benzylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1905-ethyl-6-{4-[(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1936-{4-[(3aR,4R,7aS)-4-(dimethylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 1946-(4-{(3aR,4R,7aS)-4-[benzyl(methyl)amino]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1955-ethyl-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoiridol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1966-{4-[(3aR,4R,7aS)-4-(dibenzylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1976-{4-[(3aR,4R,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 1986-{4-[(3aR,4R,6aS)-4-(dimethylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride 1996-{4-[(3aR,4R,6aS)-4-[benzyl(methyl)amino]hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride 2005-ethyl-6-{4-[(3aR,4R,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2016-{4-[(3aR,4R,6aS)-4-(dibenzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidtrifluoroacetate 2026-{4-[(3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2036-{4-[(3aR,4S,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2046-{4-[(3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2056-(4-{(3aR,7aS)-3a-[(dimethylamino)methyl]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2066-{4-[(3aR,6aS)-5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2075-ethyl-6-{4-[(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2085-ethyl-6-{4-[(3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2105-ethyl-6-{4-[(1S,5R,6R)-6-(methylamino)-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2126-{4-[(1S,5R,6S)-6-amino-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2135-ethyl-6-[4-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2146-[4-(7-amino-5-azaspiro[2.4]hept-5-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2155-ethyl-6-{4-[(3aR,5r,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate2176-(4-{3-[1-(benzylamino)cyclopropyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2186-{4-[3-(1-aminocyclobutyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 220(3aR,6aR)-2-[4-(5-carboxy-3-ethyl-6-oxo-1,6-dihydropyridin-2-yl)phenyl]hexahydrocyclopenta[c]pyrrole-3a(1H)-carboxylic acidtrifluoroacetate 2316-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]-2-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2446-{4-[(3aR,4S,7aS)-4-azidooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2456-{4-[(3aR,4S,6aS)-4-azidohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2465-ethyl-6-{4-[(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2526-[4-(7-amino-5-azaspiro[2.4]hept-5-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2545-ethyl-4-hydroxy-6-(4-{3-[(methylamino)methyl]pyrrolidin-1-yl}phenyl)-2-oxo-1,2- dihydropyridine-3-carboxylic acid hydrochloride 2565-ethyl-4-hydroxy-6-{4-[(3aR,4R,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride 2576-[4-(1,3′-bipyrrolidin-1′-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2586-{4-[(3aR,4S,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2596-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2604-hydroxy-5-methyl-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoiridol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2616-{4-[(3aR,4R,7aS)-4-(dimethylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2626-{4-[(3aR,4R,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2636-{4-[(3aR,4R,6aS)-4-(dimethylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3- carboxylicacid hydrochloride 2646-{4-[(3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2656-{4-[(3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2666-(4-{(3aR,7aS)-3a-[(dimethylamino)methyl]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride 2675-ethyl-4-hydroxy-6-{4-[(3aR,4S,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride 2685-ethyl-4-hydroxy-6-{4-[(3aR,4S,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2696-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2705-ethyl-4-hydroxy-6-{4-[(1R,5S,6s)-6-(methylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2716-{4-[(1R,5S,6s)-6-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2725-ethyl-4-hydroxy-6-[4-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2735-ethyl-4-hydroxy-6-{4-[(3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2745-ethyl-6-{4-[(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2756-{4-[3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2766-[4-(3a-cyanooctahydro-2H-isoindol-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2776-[4-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2786-[4-(2,8-diazaspiro[4.5]dec-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2796-{4-[3-(2-aminopropan-2-yl)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride 2956-[4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate 2965-ethyl-4-hydroxy-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride,and 2975-ethyl-6-{4-[(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride;wherein the form of the compound is selected from a free acid, freebase, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer,diastereomer, stereoisomer, polymorph or tautomer form thereof.

In another embodiment, the compound or a form thereof is isolated foruse.

Chemical Definitions

The chemical terms used above and throughout the description herein,unless specifically defined otherwise, shall be understood by one ofordinary skill in the art to have the following indicated meanings.

As used herein, the term “C₁₋₁₀alkyl” generally refers to saturatedhydrocarbon radicals having from one to ten carbon atoms in a straightor branched chain configuration, including, without limitation, methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl and the like. Insome embodiments, C₁₋₁₀alkyl includes C₁₋₈alkyl, C₁₋₆alkyl, C₁₋₄alkyland the like. A C₁₋₁₀alkyl radical may be optionally substituted whereallowed by available valences.

As used herein, the term “C₂₋₈alkenyl” generally refers to partiallyunsaturated hydrocarbon radicals having from two to eight carbon atomsin a straight or branched chain configuration and one or morecarbon-carbon double bonds therein, including, without limitation,ethenyl, allyl, propenyl and the like. In some embodiments, C₂₋₈alkenylincludes C₂₋₆alkenyl, C₂₋₄alkenyl and the like. A C₂₋₈alkenyl radicalmay be optionally substituted where allowed by available valences.

As used herein, the term “C₂₋₈alkynyl” generally refers to partiallyunsaturated hydrocarbon radicals having from two to eight carbon atomsin a straight or branched chain configuration and one or morecarbon-carbon triple bonds therein, including, without limitation,ethynyl, propynyl and the like. In some embodiments, C₂₋₈alkynylincludes C₂₋₆alkynyl, C₂₋₄alkynyl and the like. A C₂₋₈alkynyl radicalmay be optionally substituted where allowed by available valences.

As used herein, the term “C₁₋₈alkoxy” generally refers to saturatedhydrocarbon radicals having from one to eight carbon atoms in a straightor branched chain configuration of the formula: —O—C₁₋₈alkyl, including,without limitation, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy and the like. Insome embodiments, C₁₋₈alkoxy includes C₁₋₆alkoxy, C₁₋₄alkoxy and thelike. A C₁₋₈alkoxy radical may be optionally substituted where allowedby available valences.

As used herein, the term “C₃₋₁₄cycloalkyl” generally refers to asaturated monocyclic, bicyclic or polycyclic hydrocarbon radical,including, without limitation, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, 1H-indanyl, indenyl,tetrahydro-naphthalenyl and the like. In some embodiments,C₃₋₁₄cycloalkyl includes C₃₋₈cycloalkyl, C₅₋₈cycloalkyl, C₃₋₁₀cycloalkyland the like. A C₃₋₁₄cycloalkyl radical may be optionally substitutedwhere allowed by available valences.

As used herein, the term “C₃₋₁₄cycloalkenyl” generally refers to apartially unsaturated monocyclic, bicyclic or polycyclic hydrocarbonradical having one or more chemically stable carbon-carbon double bondstherein, including, without limitation, cyclopropenyl, cyclobutenyl,cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl and the like.In some embodiments, C₃₋₁₄cycloalkenyl includes C₃₋₈cycloalkenyl,C₅₋₈cycloalkenyl, C₃₋₁₀cycloalkenyl and the like. A C₃₋₁₄cycloalkenylradical may be optionally substituted where allowed by availablevalences.

As used herein, the term “aryl” generally refers to a monocyclic,bicyclic or polycyclic aromatic carbon atom ring structure radical,including, without limitation, phenyl, naphthyl, anthracenyl, fluorenyl,azulenyl, phenanthrenyl and the like. An aryl radical may be optionallysubstituted where allowed by available valences.

As used herein, the term “heteroaryl” generally refers to a monocyclic,bicyclic or polycyclic aromatic carbon atom ring structure radical inwhich one or more carbon atom ring members have been replaced, whereallowed by structural stability, with one or more heteroatoms, such asan O, S or N atom, including, without limitation, furanyl, thienyl (alsoreferred to as thiophenyl), pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl,isothiazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl,tetrazolyl, pyranyl, thiopyranyl, pyridinyl, pyrimidinyl, pyrazinyl,pyridazinyl, triazinyl, indolyl, indazolyl, indolizinyl, benzofuranyl,benzothienyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, 9H-purinyl,quinoxalinyl, isoindolyl, quinolinyl, isoquinolinyl, quinazolinyl,acridinyl and the like. A heteroaryl radical may be optionallysubstituted on a carbon or nitrogen atom ring member where allowed byavailable valences.

As used herein, the term “heterocyclyl” generally refers to a saturatedor partially unsaturated monocyclic, bicyclic or polycyclic carbon atomring structure radical in which one or more carbon atom ring membershave been replaced, where allowed by structural stability, with aheteroatom, such as an O, S or N atom, including, without limitation,oxiranyl, oxetanyl, azetidinyl, dihydrofuranyl, tetrahydrofuranyl,dihydrothienyl, tetrahydrothienyl, pyrrolinyl, pyrrolidinyl,dihydropyrazolyl, pyrazolinyl, pyrazolidinyl, dihydroimidazolyl,imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl,isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl,thiazolidinyl, triazolinyl, triazolidinyl, oxadiazolinyl,oxadiazolidinyl, thiadiazolinyl, thiadiazolidinyl, tetrazolinyl,tetrazolidinyl, dihydro-2H-pyranyl, dihydro-pyridinyl,tetrahydro-pyridinyl, 1,2,3,6-tetrahydropyridinyl, hexahydro-pyridinyl,dihydro-pyrimidinyl, tetrahydro-pyrimidinyl,1,4,5,6-tetrahydropyrimidinyl, dihydro-pyrazinyl, tetrahydro-pyrazinyl,dihydro-pyridazinyl, tetrahydro-pyridazinyl, piperazinyl, piperidinyl,morpholinyl, thiomorpholinyl, dihydro-triazinyl, tetrahydro-triazinyl,hexahydro-triazinyl, 1,4-diazepanyl, dihydro-indolyl, indolinyl,tetrahydro-indolyl, dihydro-indazolyl, tetrahydro-indazolyl,dihydro-isoindolyl, dihydro-benzofuranyl, tetrahydro-benzofuranyl,dihydro-benzothienyl, tetrahydro-benzothienyl, dihydro-benzimidazolyl,tetrahydro-benzimidazolyl, dihydro-benzooxazolyl,2,3-dihydrobenzoldloxazolyl, tetrahydro-benzooxazolyl,dihydro-benzooxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl,tetrahydro-benzooxazinyl, benzo[1,3]dioxolyl, benzo[1,4]dioxanyl,dihydro-purinyl, tetrahydro-purinyl, dihydro-quinolinyl,tetrahydro-quinolinyl, 1,2,3,4-tetrahydroquinolinyl,dihydro-isoquinolinyl, 3,4-dihydroisoquinolin-(1H)-yl,tetrahydro-isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl,dihydro-quinazolinyl, tetrahydro-quinazolinyl, dihydro-quinoxalinyl,tetrahydro-quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dioxolanyl,2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl, tetrahydro-2H-pyranyl,hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl,(cis)-octahydrocyclopenta[c]pyrrolyl,hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,5H-pyrrolo[3,4-b]pyridin-(7H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,(4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9-tetrahydro-1H-carbazolyl,1,2,3,4-tetrahydropyrazino[1,2-a]indolyl,2,3-dihydro-1H-pyrrolo[1,2-a]indolyl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,(3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,(3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl,(3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl,2-azabicyclo[2.2.1]hept-5-enyl, 3-azabicyclo[3.1.0]hexanyl,3,6-diazabicyclo[3.1.0]hexanyl, (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,(1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,(1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl,2,8-diazaspiro[4.5]decanyl and the like. A heterocyclyl radical may beoptionally substituted on a carbon or nitrogen atom ring member whereallowed by available valences.

As used herein, the term “C₂₋₈alkenyl-amino” refers to a radical of theformula: —NH—C₂₋₈alkenyl.

As used herein, the term “(C₂₋₈alkenyl)₂-amino” refers to a radical ofthe formula: —N(C₂₋₈alkenyl)₂.

As used herein, the term “C₂₋₈alkenyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH—C₂₋₈alkenyl.

As used herein, the term “(C₂₋₈alkenyl)₂-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N(C₂₋₈alkenyl)₂.

As used herein, the term “C₁₋₈alkoxy-C₁₋₈alkyl” refers to a radical ofthe formula: —C₁₋₈alkyl-O—C₁₋₈alkyl.

As used herein, the term “C₁₋₈alkoxy-C₁₋₈alkyl-amino” refers to aradical of the formula: —O—C₁₋₈alkyl-NH—C₁₋₈alkyl-O—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino” refers to aradical of the formula: —N(C₁₋₈alkyl-O—C₁₋₈alkyl)₂.

As used herein, the term “C₁₋₈alkoxy-C₁₋₈alkyl-amino-C₁₋₈alkyl” refersto a radical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-O—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N(C₁₋₈alkyl-O—C₁₋₈alkyl)₂.

As used herein, the term “(C₁₋₈alkoxy-C₁₋₈alkyl, C₁₋₈alkyl)-amino”refers to a radical of the formula:—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-O—C₁₋₈alkyl)].

As used herein, the term “(C₁₋₈alkoxy-C₁₋₈alkyl,C₁₋₈alkyl)-amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-O—C₁₋₈alkyl)].

As used herein, the term “C₁₋₈alkoxy-carbonyl” refers to a radical ofthe formula: —C(O)—O—C₁₋₈alkyl.

As used herein, the term “C₁₋₈alkyl-amino” refers to a radical of theformula: —NH—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl)₂-amino” refers to a radical of theformula: —N(C₁₋₈alkyl)₂.

As used herein, the term “C₁₋₈alkyl-amino-C₁₋₈alkyl” refers to a radicalof the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N(C₁₋₈alkyl)₂.

As used herein, the term “C₁₋₈alkyl-amino-C₁₋₈alkyl-amino” refers to aradical of the formula: —NH—C₁₋₈alkyl-NH—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino” refers toa radical of the formula: —NH—C₁₋₈alkyl-N(C₁₋₈alkyl)₂.

As used herein, the term “C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-NH—C₁₋₈alkyl-NH—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-NH—C₁₋₈alkyl-N(C₁₋₈alkyl)₂.

As used herein, the term “(C₁₋₈alkyl-amino-C₁₋₈alkyl, C₁₋₈alkyl)amino”refers to a radical of the formula:—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-NH—C₁₋₈alkyl)].

As used herein, the term “[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino” refers to a radical of the formula:—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-N(C₁₋₈alkyl)₂)].

As used herein, the term “(C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl.

As used herein, the term “[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-N(C₁₋₈alkyl)₂)].

As used herein, the term “C₁₋₈alkyl-amino-carbonyl” refers to a radicalof the formula: —C(O)—NH—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl)₂-amino-carbonyl” refers to aradical of the formula: —C(O)—N(C₁₋₈alkyl)₂.

As used herein, the term “C₁₋₈alkyl-carbonyl” refers to a radical of theformula: —C(O)—C₁₋₈alkyl.

As used herein, the term “C₁₋₈alkyl-carbonyl-amino” refers to a radicalof the formula: —NH—C(O)—C₁₋₈alkyl.

As used herein, the term “(C₁₋₈alkyl-carbonyl,C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C(O)—C₁₋₈alkyl)].

As used herein, the term “C₁₋₈alkyl-thio” refers to a radical of theformula: —S—C₁₋₈alkyl.

As used herein, the term “C₂₋₈alkynyl-C₁₋₈alkyl” refers to a radical ofthe formula: —C₁₋₈alkyl-C₂₋₈alkynyl.

As used herein, the term “C₂₋₈alkynyl-amino” refers to a radical of theformula: —NH—C₂₋₈alkynyl.

As used herein, the term “(C₂₋₈alkynyl)₂-amino” refers to a radical ofthe formula: —N(C₂₋₈alkynyl)₂.

As used herein, the term “C₂₋₈alkynyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH—C₂₋₈alkynyl.

As used herein, the term “(C₂₋₈alkynyl)₂-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N(C₂₋₈alkynyl)₂.

As used herein, the term “amino” refers to a radical of the formula:—NH₂.

As used herein, the term “amino-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-NH₂.

As used herein, the term “amino-C₁₋₈alkyl-amino” refers to a radical ofthe formula: —NH—C₁₋₈alkyl-NH₂.

As used herein, the term “(amino-C₁₋₈alkyl)₂-amino” refers to a radicalof the formula: —N(C₁₋₈alkyl-NH₂)₂.

As used herein, the term “amino-C₁₋₈alkyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-NH₂.

As used herein, the term “(amino-C₁₋₈alkyl, C₁₋₈alkyl)amino” refers to aradical of the formula: —N[(C₁₋₈alkyl)(—C₁₋₈alkyl-NH₂)].

As used herein, the term “(amino-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-NH₂)].

As used herein, the term “amino-carbonyl” refers to a radical of theformula: —C(O)—NH₂.

As used herein, the term “aryl-C₁₋₈alkoxy” refers to a radical of theformula: —O—C₁₋₈alkyl-aryl.

As used herein, the term “aryl-C₁₋₈alkoxy-carbonyl-amino” refers to aradical of the formula: —NH—C(O)—O—C₁₋₈alkyl-aryl.

As used herein, the term “aryl-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-aryl.

As used herein, the term “aryl-C₁₋₈alkyl-amino” refers to a radical ofthe formula: —NH—C₁₋₈alkyl-aryl.

As used herein, the term “(aryl-C₁₋₈alkyl)₂-amino” refers to a radicalof the formula: —N[(—C₁₋₈alkyl-aryl)₂].

As used herein, the term “aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-aryl.

As used herein, the term “(aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N[(—C₁₋₈alkyl-aryl)₂].

As used herein, the term “(aryl, C₁₋₈alkyl)amino” refers to a radical ofthe formula: —N[(C₁₋₈alkyl)(aryl)].

As used herein, the term “(aryl, C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N[(C₁₋₈alkyl)(aryl)].

As used herein, the term “(aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino” refers to aradical of the formula: —N[(C₁₋₈alkyl)(—C₁₋₈alkyl-aryl)].

As used herein, the term “(aryl-C₁₋₈alkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-aryl)].

As used herein, the term “aryl-amino” refers to a radical of theformula: —NH-aryl.

As used herein, the term “(aryl)₂-amino” refers to a radical of theformula: —N[(aryl)₂].

As used herein, the term “aryl-amino-C₁₋₈alkyl” refers to a radical ofthe formula: —C₁₋₈alkyl-NH-aryl.

As used herein, the term “(aryl)₂-amino-C₁₋₈alkyl” refers to a radicalof the formula: —C₁₋₈alkyl-N[(aryl)₂].

As used herein, the term “aryl-amino-carbonyl” refers to a radical ofthe formula: —C(O)—NH-aryl.

As used herein, the term “azido” refers to a radical of the formula:—N═N⁺═N⁻.

As used herein, the term “carboxyl” refers to a radical of the formula:—COOH, —C(O)OH or —CO₂H.

As used herein, the term “(carboxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-carbonyl-amino” refers to a radical of the formula:—NH—C(O)—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-CO₂H)].

As used herein, the term “C₃₋₁₄cycloalkyl-C₁₋₈alkoxy” refers to aradical of the formula: —O—C₁₋₈alkyl-C₃₋₁₄cycloalkyl.

As used herein, the term “C₃₋₁₄cycloalkyl-C₁₋₈alkyl” refers to a radicalof the formula: —C₁₋₈alkyl-C₃₋₁₄cycloalkyl.

As used herein, the term “C₃₋₁₄cycloalkyl-amino” refers to a radical ofthe formula: —NH—C₃₋₁₄cycloalkyl.

As used herein, the term “C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH—C₃₋₁₄cycloalkyl.

As used herein, the term “(C₃₋₁₄cycloalkyl)₂-amino-C₁₋₈alkyl” refers toa radical of the formula: —C₁₋₈alkyl-N[(—C₃₋₁₄cycloalkyl)₂].

As used herein, the term “C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-NH—C₁₋₈alkyl-C₃₋₁₄cycloalkyl.

As used herein, the term “(C₃₋₁₄cycloalkyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(—C₁₋₈alkyl-C₃₋₁₄cycloalkyl)₂].

As used herein, the term “(C₃₋₁₄cycloalkyl, C₁₋₈alkyl)amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(C₃₋₁₄cycloalkyl)].

As used herein, the term “(C₃₋₁₄cycloalkyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-C₃₋₁₄cycloalkyl)].

As used herein, the term “C₃₋₁₄cycloalkyl-oxy” refers to a radical ofthe formula: —O—C₃₋₁₄cycloalkyl.

As used herein, the term “formyl” refers to a radical of the formula:—C(O)—H.

As used herein, the term “formyl-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-C(O)—H, including, without limitation, formylmethyl(also referred to as 2-oxoethyl or formylmethyl), 2-formyl-ethyl (alsoreferred to as 3-oxopropyl or formylethyl), 3-formyl-propyl (alsoreferred to as 4-oxobutyl or formylpropyl), 4-formyl-butyl (alsoreferred to as 5-oxopentyl or formylpropyl) and the like.

As used herein, the term “halo” or “halogen” generally refers to ahalogen atom radical, including fluoro, chloro, bromo and iodo.

As used herein, the term “halo-C₁₋₈alkoxy” refers to a radical of theformula: —O—C₁₋₈alkyl-halo, wherein C₁₋₈alkyl may be partially orcompletely substituted where allowed by available valences with one ormore halogen atoms, including, without limitation, fluoromethoxy,difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy ortrifluoroethoxy and the like. In some embodiments, difluoroethoxyincludes 2,2-difluoroethoxy, 1,2-difluoroethoxy or 1,1-difluoroethoxyand the like. In some embodiments, halo-C₁₋₈alkoxy includeshalo-C₁₋₆alkoxy, halo-C₁₋₄alkoxy and the like.

As used herein, the term “halo-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-halo, wherein C₁₋₈alkyl may be partially orcompletely substituted where allowed by available valences with one ormore halogen atoms, including, without limitation, fluoromethyl,difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl,trifluoroethyl, fluoroisopropyl, difluoroisopropyl, trifluoroisopropyl,fluoro-tert-butyl, difluoro-tert-butyl, trifluoro-tert-butyl and thelike. In some embodiments, difluoroethyl includes 2,2-difluoroethyl,1,2-difluoroethyl or 1,1-difluoroethyl and the like; difluoroisopropylincludes 1,3-difluoropropan-2-yl and the like; trifluoroisopropylincludes 1,1,1-trifluoropropan-2-yl and the like; trifluoro-tert-butylincludes 1,1,1-trifluoro-2-methylpropan-2-yl and the like. In someembodiments, halo-C₁₋₈alkyl includes halo-C₁₋₆alkyl, halo-C₁₋₄alkyl andthe like.

As used herein, the term “halo-C₁₋₈alkyl-amino” refers to a radical ofthe formula: —NH—C₁₋₈alkyl-halo.

As used herein, the term “(halo-C₁₋₈alkyl-amino” refers to a radical ofthe formula: —N(C₁₋₈alkyl-halo)₂.

As used herein, the term “halo-C₁₋₈alkyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —NH—C₁₋₈alkyl-halo.

As used herein, the term “(halo-C₁₋₈alkyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N(C₁₋₈alkyl-halo)₂.

As used herein, the term “heteroaryl-C₁₋₈alkyl” refers to a radical ofthe formula: —C₁₋₈alkyl-heteroaryl.

As used herein, the term “heteroaryl-amino” refers to a radical of theformula: —NH-heteroaryl.

As used herein, the term “(heteroaryl)₂-amino” refers to a radical ofthe formula: —N[(heteroaryl)₂].

As used herein, the term “heteroaryl-C₁₋₈alkyl-amino” refers to aradical of the formula: —NH—C₁₋₈alkyl-heteroaryl.

As used herein, the term “(heteroaryl-C₁₋₈alkyl-amino” refers to aradical of the formula: —N[(—C₁₋₈alkyl-heteroaryl)₂].

As used herein, the term “heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl” refersto a radical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-heteroaryl.

As used herein, the term “(heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl” refersto a radical of the formula: —C₁₋₈alkyl-N[(—C₁₋₈alkyl-heteroaryl)₂].

As used herein, the term “(heteroaryl-C₁₋₈alkyl, C₁₋₈alkyl)amino” refersto a radical of the formula: —N[(—C₁₋₈alkyl)(—C₁₋₈alkyl-heteroaryl)].

As used herein, the term “(heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-heteroaryl)].

As used herein, the term “heterocyclyl-C₁₋₈alkoxy” refers to a radicalof the formula: —O—C₁₋₈alkyl-heterocyclyl.

As used herein, the term “heterocyclyl-C₁₋₈alkyl” refers to a radical ofthe formula: —C₁₋₈alkyl-heterocyclyl.

As used herein, the term “heterocyclyl-amino” refers to a radical of theformula: —NH-heterocyclyl.

As used herein, the term “(heterocyclyl)₂-amino” refers to a radical ofthe formula: —N[(heterocyclyl)₂].

As used herein, the term “heterocyclyl-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-NH-heterocyclyl.

As used herein, the term “(heterocyclyl)₂-amino-C₁₋₈alkyl” refers to aradical of the formula: —C₁₋₈alkyl-N[(heterocyclyl)₂].

As used herein, the term “heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl” refersto a radical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-heterocyclyl.

As used herein, the term “(heterocyclyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(—C₁₋₈alkyl-heterocyclyl)₂].

As used herein, the term “(heterocyclyl, C₁₋₈alkyl)amino” refers to aradical of the formula: —N[(C₁₋₈alkyl)(heterocyclyl)].

As used herein, the term “(heterocyclyl, C₁₋₈alkyl)amino-C₁₋₈alkyl”refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(heterocyclyl)].

As used herein, the term “(heterocyclyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(—C₁₋₈alkyl-heterocyclyl)].

As used herein, the term “(heterocyclyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-N[(heterocyclyl)(—C₁₋₈alkyl-C₃₋₁₄cycloalkyl)].

As used herein, the term “heterocyclyl-carbonyl” refers to a radical ofthe formula: —C(O)-heterocyclyl.

As used herein, the term “heterocyclyl-carbonyl-oxy” refers to a radicalof the formula: —O—C(O)-heterocyclyl.

As used herein, the term “heterocyclyl-oxy” refers to a radical of theformula: —O-heterocyclyl.

As used herein, the term “heterocyclyl-oxy-amino” refers to a radical ofthe formula: —NH—O-heterocyclyl.

As used herein, the term “(heterocyclyl-oxy)₂-amino” refers to a radicalof the formula: —N[(—O-heterocyclyl)₂].

As used herein, the term “(heterocyclyl-oxy, C₁₋₈alkyl)amino” refers toa radical of the formula: —N[(—C₁₋₈alkyl)(—O-heterocyclyl)].

As used herein, the term “(heterocyclyl-oxy-C₁₋₈alkyl, C₁₋₈alkyl)amino”refers to a radical of the formula:—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-O-heterocyclyl)].

As used herein, the term “hydroxyl-C₁₋₈alkoxy” refers to a radical ofthe formula: —O—C₁₋₈alkyl-OH, wherein C₁₋₈alkyl may be partially orcompletely substituted where allowed by available valences with one ormore hydroxyl radicals.

As used herein, the term “hydroxyl-C₁₋₈alkyl” refers to a radical of theformula: —C₁₋₈alkyl-OH, wherein C₁₋₈alkyl may be partially or completelysubstituted where allowed by available valences with one or morehydroxyl radicals.

As used herein, the term “hydroxyl-amino” refers to a radical of theformula: —NH—OH.

As used herein, the term “hydroxyl-C₁₋₈alkyl-amino” refers to a radicalof the formula: —NH—C₁₋₈alkyl-OH, wherein C₁₋₈alkyl may be partially orcompletely substituted where allowed by available valences with one ormore hydroxyl radicals.

As used herein, the term “(hydroxyl-C₁₋₈alkyl-amino” refers to a radicalof the formula: —N(C₁₋₈alkyl-OH)₂, wherein C₁₋₈alkyl may be partially orcompletely substituted where allowed by available valences with one ormore hydroxyl radicals.

As used herein, the term “hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl” refers toa radical of the formula: —C₁₋₈alkyl-NH—C₁₋₈alkyl-OH, wherein C₁₋₈alkylmay be partially or completely substituted where allowed by availablevalences with one or more hydroxyl radicals.

As used herein, the term “hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl-amino”refers to a radical of the formula: —NH—C₁₋₈alkyl-NH—C₁₋₈alkyl-OH,wherein C₁₋₈alkyl may be partially or completely substituted whereallowed by available valences with one or more hydroxyl radicals.

As used herein, the term “(hydroxyl-C₁₋₈alkyl, C₁₋₈alkyl)amino” refersto a radical of the formula: —N[(C₁₋₈alkyl)(C₁₋₈alkyl-OH)], whereinC₁₋₈alkyl may be partially or completely substituted where allowed byavailable valences with one or more hydroxyl radicals.

As used herein, the term “(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl” refers to a radical of the formula:—C₁₋₈alkyl-N[(C₁₋₈alkyl)(C₁₋₈alkyl-OH)], wherein C₁₋₈alkyl may bepartially or completely substituted where allowed by available valenceswith one or more hydroxyl radicals.

As used herein, the term “(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl-amino” refers to a radical of the formula:—NH—C₁₋₈alkyl-N[(C₁₋₈alkyl)(C₁₋₈alkyl-OH)], wherein C₁₋₈alkyl may bepartially or completely substituted where allowed by available valenceswith one or more hydroxyl radicals.

As used herein, the term “Rhydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, C₁₋₈alkyl)amino” refers to a radical of theformula: —N[(C₁₋₈alkyl)(—C₁₋₈alkyl-N[(—C₁₋₈alkyl)(C₁₋₈alkyl-OH)])],wherein C₁₋₈alkyl may be partially or completely substituted whereallowed by available valences with one or more hydroxyl radicals.

As used herein, the term “(hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl)amino” refers to a radical of the formula:—N[(C₁₋₈alkyl)(—C₁₋₈alkyl-NH—C₁₋₈alkyl-OH)], wherein C₁₋₈alkyl may bepartially or completely substituted where allowed by available valenceswith one or more hydroxyl radicals.

As used herein, the term “substituent” means positional variables on theatoms of a core molecule that are substituted at a designated atomposition, replacing one or more hydrogens on the designated atom,provided that the designated atom's normal valency is not exceeded, andthat the substitution results in a stable compound. Combinations ofsubstituents and/or variables are permissible only if such combinationsresult in stable compounds. A person of ordinary skill in the art shouldnote that any carbon as well as heteroatom with valences that appear tobe unsatisfied as described or shown herein is assumed to have asufficient number of hydrogen atom(s) to satisfy the valences describedor shown.

As used herein, the term “and the like,” with reference to thedefinitions of chemical terms provided herein, means that variations inchemical structures that could be expected by one skilled in the artinclude, without limitation, isomers (including chain, branching orpositional structural isomers), hydration of ring systems (includingsaturation or partial unsaturation of monocyclic, bicyclic or polycyclicring structures) and all other variations where allowed by availablevalences which result in a stable compound.

For the purposes of this description, where one or more substituentvariables for a compound of Formula (I) encompass functionalitiesincorporated into a compound of Formula (I), each functionalityappearing at any location within the disclosed compound may beindependently selected, and as appropriate, independently and/oroptionally substituted.

As used herein, the terms “independently selected,” or “each selected”refer to functional variables in a substituent list that may occur morethan once on the structure of Formula (I), the pattern of substitutionat each occurrence is independent of the pattern at any otheroccurrence. Further, the use of a generic substituent variable on anyformula or structure for a compound described herein is understood toinclude the replacement of the generic substituent with speciessubstituents that are included within the particular genus, e.g., arylmay be replaced with phenyl or naphthalenyl and the like, and that theresulting compound is to be included within the scope of the compoundsdescribed herein.

As used herein, the term “each instance of” when used in a phrase suchas “ . . . aryl, aryl-C₁₋₈alkyl, heterocyclyl andheterocyclyl-C₁₋₈alkyl, wherein each instance of aryl and heterocyclylis optionally substituted with one or two substituents . . . ” (emphasisadded) is intended to optionally include substitution on each appearanceof aryl and heterocyclyl, whether the ring is a primary or secondarysubstituent, that is, where the the aryl and heterocyclyl rings are theprimary (first) substituent or where the primary substituent isC₁₋₈alkyl and the aryl and heterocyclyl rings are the secondary (second)substituent, as in, for example, aryl-C₁₋₈alkyl andheterocyclyl-C₁₋₈alkyl.

As used herein, the term “optionally substituted” means optionalsubstitution with the specified substituent variables, groups, radicalsor moieties.

As used herein, the terms “stable compound” or “stable structure” mean acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture and formulations thereof intoan efficacious therapeutic agent.

Compound names used herein were obtained using the ACD Labs Index Namesoftware provided by ACD Labs; and/or, were provided using the Autonomfunction of ChemDraw Ultra provided by CambridgeSoft. When the compoundname disclosed herein conflicts with the structure depicted, thestructure shown will supercede the use of the name to define thecompound intended.

Compound Forms

As used herein, the term “a compound of Formula (Ia),” as definedpreviously, refer to a sub-genus of the compound of Formula (I) or aform thereof. Rather than repeat embodiments for a compound of Formula(Ia), in certain embodiments, the term “a compound of Formula (I) or aform thereof” is used to refer to a compound of Formula (Ia) or a formthereof. Thus, embodiments and references to “a compound of Formula (I)”are intended to include compounds of Formula (Ia).

As used herein, the term “form” means a compound of Formula (I) isolatedfor use selected from a free acid, free base, salt, hydrate, solvate,clathrate, isotopologue, racemate, enantiomer, diastereomer,stereoisomer, polymorph or tautomer form thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a free acid, free base or salt thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is an isotopologue thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a stereoisomer, racemate, enantiomer or diastereomerthereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a tautomer thereof.

In certain embodiments described herein, the form of the compound ofFormula (I) is a pharmaceutically acceptable form.

In certain embodiments described herein, the compound of Formula (I) ora form thereof is isolated for use.

As used herein, the term “isolated” means the physical state of acompound of Formula (I) after being isolated and/or purified from asynthetic process (e.g., from a reaction mixture) or natural source orcombination thereof according to an isolation or purification process orprocesses described herein or which are well known to the skilledartisan (e.g., chromatography, recrystallization and the like) insufficient purity to be characterizable by standard analyticaltechniques described herein or well known to the skilled artisan.

As used herein, the term “protected” means that a functional group in acompound of Formula (I) is in a form modified to preclude undesired sidereactions at the protected site when the compound is subjected to areaction. Suitable protecting groups will be recognized by those withordinary skill in the art as well as by reference to standard textbookssuch as, for example, T. W. Greene et al, Protective Groups in OrganicSynthesis (1991), Wiley, New York.

Prodrugs and solvates of the compounds described herein are alsocontemplated.

As used herein, the term “prodrug” means a form of an instant compound(e.g., a drug precursor) that is transformed in vivo to yield an activecompound of Formula (I) or a form thereof. The transformation may occurby various mechanisms (e.g., by metabolic and/or non-metabolic chemicalprocesses), such as, for example, by hydrolysis and/or metabolism inblood, liver and/or other organs and tissues. A discussion of the use ofprodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as NovelDelivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and inBioreversible Carriers in Drug Design, ed. Edward B. Roche, AmericanPharmaceutical Association and Pergamon Press, 1987.

In one example, when a compound of Formula (I) or a form thereofcontains a carboxylic acid functional group, a prodrug can comprise anester formed by the replacement of the hydrogen atom of the acid groupwith a functional group such as alkyl and the like. In another example,when a compound of Formula (I) or a form thereof contains an alcoholfunctional group, a prodrug can be formed by the replacement of thehydrogen atom of the alcohol group with a functional group such as alkylor carbonyloxy and the like. In another example, when a compound ofFormula (I) or a form thereof contains an amine functional group, aprodrug can be formed by the replacement of one or more amine hydrogenatoms with a functional group such as alkyl or substituted carbonyl.

One or more compounds described herein may exist in unsolvated as wellas solvated forms with pharmaceutically acceptable solvents such aswater, ethanol, and the like, and the description herein is intended toembrace both solvated and unsolvated forms.

As used herein, the term “solvate” means a physical association of acompound described herein with one or more solvent molecules. Thisphysical association involves varying degrees of ionic and covalentbonding, including hydrogen bonding. In certain instances the solvatewill be capable of isolation, for example when one or more solventmolecules are incorporated in the crystal lattice of the crystallinesolid. As used herein, “solvate” encompasses both solution-phase andisolatable solvates. Non-limiting examples of suitable solvates includeethanolates, methanolates, and the like.

One or more compounds described herein may optionally be converted to asolvate. Preparation of solvates is generally known. The preparation ofsolvates of the antifungal fluconazole in ethyl acetate as well as fromwater has been described (see, M. Caira et al, J. Pharmaceutical Sci.,93(3), 601-611 (2004)). Similar preparations of solvates, hemisolvate,hydrates and the like have also been described (see, E. C. van Tonder etal, AAPS PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham etal, Chem. Commun., 603-604 (2001)). A typical, non-limiting processinvolves dissolving a compound in a desired amount of the desiredsolvent (organic or water or mixtures thereof) at a higher than ambienttemperature, and cooling the solution at a rate sufficient to formcrystals which are then isolated by standard methods. Analyticaltechniques such as, for example infrared spectroscopy, show the presenceof the solvent (or water) in the crystals as a solvate (or hydrate).

As used herein, the term “hydrate” means a solvate wherein the solventmolecule is water.

The compounds of Formula (I) can form salts, which are intended to beincluded within the scope of this description. Reference to a compoundof Formula (I) herein is understood to include reference to saltsthereof, unless otherwise indicated. The term “salt(s)”, as employedherein, denotes acidic salts formed with inorganic and/or organic acids,as well as basic salts formed with inorganic and/or organic bases. Inaddition, when a compound of Formula (I) contains both a basic moiety,such as, but not limited to a pyridine or imidazole, and an acidicmoiety, such as, but not limited to a carboxylic acid, zwitterions(“inner salts”) may be formed and are included within the term “salt(s)”as used herein.

The term “pharmaceutically acceptable salt(s)”, as used herein, meansthose salts of compounds described herein that are safe and effective(i.e., non-toxic, physiologically acceptable) for use in mammals andthat possess biological activity, although other salts are also useful.Salts of the compounds of the Formula (I) may be formed, for example, byreacting a compound of Formula (I) with an amount of acid or base, suchas an equivalent amount, in a medium such as one in which the saltprecipitates or in an aqueous medium followed by lyophilization.

Pharmaceutically acceptable salts include one or more salts of acidic orbasic groups present in compounds described herein. Embodiments of acidaddition salts include, and are not limited to, acetate, acid phosphate,ascorbate, benzoate, benzenesulfonate, bisulfate, bitartrate, borate,butyrate, chloride, citrate, camphorate, camphorsulfonate,ethanesulfonate, formate, fumarate, gentisinate, gluconate, glucaronate,glutamate, hydrobromide, hydrochloride, dihydrochloride, hydroiodide,isonicotinate, lactate, maleate, methanesulfonate, naphthalenesulfonate,nitrate, oxalate, pamoate, pantothenate, phosphate, propionate,saccharate, salicylate, succinate, sulfate, tartrate, thiocyanate,toluenesulfonate (also known as tosylate), trifluoroacetate salts andthe like. Certain embodiments of acid addition salts include chloride,hydrobromide, hydrochloride, dihydrochloride, acetate or trifluoroaceticacid salts.

Additionally, acids which are generally considered suitable for theformation of pharmaceutically useful salts from basic pharmaceuticalcompounds are discussed, for example, by P. Stahl et al, Camille G.(eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use.(2002) Zurich: Wiley-VCH; S. Berge et al, Journal of PharmaceuticalSciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics(1986) 33, 201-217; Anderson et al, The Practice of Medicinal Chemistry(1996), Academic Press, New York; and in The Orange Book (Food & DrugAdministration, Washington, D.C. on their website). These disclosuresare incorporated herein by reference thereto.

Suitable basic salts include, but are not limited to, aluminum,ammonium, calcium, lithium, magnesium, potassium, sodium, zinc, anddiethanolamine salts. Certain compounds of described herein can alsoform pharmaceutically acceptable salts with organic bases (for example,organic amines) such as, but not limited to, dicyclohexylamines, t-butylamines and the like, and with various amino acids such as, but notlimited to, arginine, lysine and the like. Basic nitrogen-containinggroups may be quarternized with agents such as lower alkyl halides(e.g., methyl, ethyl, and butyl chlorides, bromides and iodides),dialkyl sulfates (e.g., dimethyl, diethyl, and dibutyl sulfates), longchain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides andiodides), aralkyl halides (e.g., benzyl and phenethyl bromides), andothers.

All such acid salts and base salts are intended to be included withinthe scope of pharmaceutically acceptable salts as described herein. Inaddition, all such acid and base salts are considered equivalent to thefree forms of the corresponding compounds for purposes of thisdescription.

Pharmaceutically acceptable prodrugs of compounds of Formula (I) or aform thereof include those compounds substituted with one or more of thefollowing groups: carboxylic acid esters, sulfonate esters, amino acidesters phosphonate esters and mono-, di- or triphosphate esters or alkylsubstituents, where appropriate. As described herein, it is understoodby a person of ordinary skill in the art that one or more of suchsubstituents may be used to provide a compound of Formula (I) or a formthereof as a prodrug.

Compounds of Formula (I), and forms thereof, may further exist in atautomeric form (for example, as an amide or imino ether). All suchtautomeric forms are contemplated and intended to be included within thescope of the compounds of Formula (I) or a form thereof as describedherein.

The compounds of Formula (I) may contain asymmetric or chiral centers,and, therefore, exist in different stereoisomeric forms. The presentdescription is intended to include all stereoisomeric forms of thecompounds of Formula (I) as well as mixtures thereof, including racemicmixtures.

The compounds described herein may include one or more chiral centers,and as such may exist as racemic mixtures (R/S) or as substantially pureenantiomers and diastereomers.

The compounds may also exist as substantially pure (R) or (S)enantiomers (when one chiral center is present). In one embodiment, thecompounds described herein are (S) isomers and may exist asenantiomerically pure compositions substantially comprising only the (S)isomer. In another embodiment, the compounds described herein are (R)isomers and may exist as enantiomerically pure compositionssubstantially comprising only the (R) isomer. As one of skill in the artwill recognize, when more than one chiral center is present, thecompounds described herein may also exist as a (R,R), (R,S), (S,R) or(S,S) isomer, as defined by IUPAC Nomenclature Recommendations.

As used herein, the term “substantially pure” refers to compoundsconsisting substantially of a single isomer in an amount greater than orequal to 90%, in an amount greater than or equal to 92%, in an amountgreater than or equal to 95%, in an amount greater than or equal to 98%,in an amount greater than or equal to 99%, or in an amount equal to 100%of the single isomer.

In one aspect of the description, a compound of Formula (I) is asubstantially pure (S) enantiomer present in an amount greater than orequal to 90%, in an amount greater than or equal to 92%, in an amountgreater than or equal to 95%, in an amount greater than or equal to 98%,in an amount greater than or equal to 99%, or in an amount equal to100%.

In one aspect of the description, a compound of Formula (I) is asubstantially pure (R) enantiomer present in an amount greater than orequal to 90%, in an amount greater than or equal to 92%, in an amountgreater than or equal to 95%, in an amount greater than or equal to 98%,in an amount greater than or equal to 99%, or in an amount equal to100%.

As used herein, a “racemate” is any mixture of isometric forms that arenot “enantiomerically pure”, including mixtures such as, withoutlimitation, in a ratio of about 50/50, about 60/40, about 70/30, orabout 80/20.

In addition, the present description embraces all geometric andpositional isomers. For example, if a compound of Formula (I)incorporates a double bond or a fused ring, both the cis- andtrans-forms, as well as mixtures, are embraced within the scope of thedescription. Diastereomeric mixtures can be separated into theirindividual diastereomers on the basis of their physical chemicaldifferences by methods well known to those skilled in the art, such as,for example, by chromatography and/or fractional crystallization.Enantiomers can be separated by use of chiral HPLC column or otherchromatographic methods known to those skilled in the art. Enantiomerscan also be separated by converting the enantiomeric mixture into adiastereomeric mixture by reaction with an appropriate optically activecompound (e.g., chiral auxiliary such as a chiral alcohol or Mosher'sacid chloride), separating the diastereomers and converting (e.g.,hydrolyzing) the individual diastereomers to the corresponding pureenantiomers. Also, some of the compounds of Formula (I) may beatropisomers (e.g., substituted biaryls) and are considered as part ofthis description.

It is also possible that the compounds of Formula (I) may exist indifferent tautomeric forms, and all such forms are embraced within thescope of the description. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the scope of thisdescription.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this description, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). For example, ifa compound of Formula (I) incorporates a double bond or a fused ring,both the cis- and trans-forms, as well as mixtures thereof, are embracedherein. Also, for example, all keto-enol and imine-enamine forms of thecompounds are included herein. Individual stereoisomers of the compoundsdescribed herein may, for example, be substantially free of otherisomers, or may be present in a racemic mixture, as described supra.

The use of the terms “salt”, “solvate”, “ester”, “prodrug” and the like,is intended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates, isotopologues or prodrugs of the instant compounds.

The term “isotopologue” refers to isotopically-enriched compoundsdescribed herein which are identical to those recited herein, but forthe fact that one or more atoms are replaced by an atom having an atomicmass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds described herein include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine, such as H², H³,C¹³, C¹⁴, N¹⁵, O¹⁸, O¹⁷, P³¹, P³², S³⁵, F¹⁸, Cl³⁵ and Cl³⁶,respectively, each of which are also within the scope of thisdescription.

Certain isotopically-enriched compounds described herein (e.g., thoselabeled with H³ and C¹⁴) are useful in compound and/or substrate tissuedistribution assays. Tritiated (i.e., H³) and carbon-14 (i.e., C¹⁴)isotopes are particularly preferred for their ease of preparation anddetectability. Further, substitution with heavier isotopes such asdeuterium (i.e., H²) may afford certain therapeutic advantages resultingfrom greater metabolic stability (e.g., increased in vivo half-life orreduced dosage requirements) and hence may be preferred in somecircumstances.

Polymorphic crystalline and amorphous forms of the compounds of Formula(I), and of the salts, solvates, hydrates, esters and prodrugs of thecompounds of Formula (I), are further intended to be included in thepresent description.

Use of Compounds

The present description further relates to uses of the compound ofFormula (I) and methods of treating or ameliorating a bacterialinfection, or of treating or ameliorating a multi-drug resistant (MDR)bacterial infection.

The present description further relates to uses of the compound ofFormula (I) having activity toward wild-type and MDR bacteria. Thepresent description also relates to uses of the compound of Formula (I)having activity against quinolone-resistant Gram-negative strains(including MDR strains) as well as antibacterial activity to MDRresistant Gram-positive pathogens (including MRSA strains). The presentdescription also relates to uses of the compound of Formula (I) havingselectivity between bacterial topoisomerase IV and DNA gyrase enzymeinhibition compared to human topoisomerase II enzyme inhibition. Thepresent description further relates to uses of the compound of Formula(I) that may be combined with known antibacterial agents to provideadditive or synergistic activity, thus enabling the development of acombination product for the treatment of Gram-negative (especially MDRstrains) and Gram-positive infections.

The compounds of the present description inhibit the clinicallyvalidated bacterial targets DNA gyrase and topoisomerase IV, and, thus,may be used for the treatment of infections caused by Gram-negative andGram-positive pathogens. The instant compounds possess in vitroantibacterial activity against a wide spectrum of bacteria which havedeveloped resistance to almost all known treatments, including MDRGram-negative and MDR Gram-positive pathogens and successfully effectthe treatment of bacterial infections compared to current antibacterialagents that target the same enzymes. The compounds are also effective invivo and lack cellular toxicity. In addition to monotherapeutic use, theinstant compounds are amenable to combination therapy with currentstandards of care, having demonstrated additive and synergistic activitywith one or more fluoroquinolone based antibacterial agents. Thedemonstrated additive and synergistic activity of the compoundsindicates a mechanistically alternate binding in conjunction with theDNA gyrase and topoisomerase IV targets.

Accordingly, the present description relates to methods of using acompound of Formula (I) for treating or ameliorating a bacterialinfection, or for using a compound of Formula (I) for treating orameliorating a multidrug resistant bacterial infection. In accordancewith the present description, compounds that selectively treat orameliorate a bacterial infection have been identified and methods ofusing these compounds for treating or ameliorating a bacterial infectionor disorders or symptoms associated therewith are provided.

One embodiment of the present description relates to a method oftreating or ameliorating a bacterial infection in a subject in needthereof comprising administering an effective amount of a compound ofFormula (I) or a form thereof to the subject.

An embodiment of the present description relates to a method of treatingor ameliorating a bacterial infection resulting from a bacteria that isa Gram-negative or Gram-positive type in a subject in need thereofcomprising administering an effective amount of the compound of Formula(I) or a form thereof to the subject.

An embodiment of the present description relates to a method of treatingor ameliorating a bacterial infection resulting from a bacteria that isa resistant Gram-negative or Gram-positive type in a subject in needthereof comprising administering an effective amount of the compound ofFormula (I) or a form thereof to the subject.

One embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof for treating or ameliorating abacterial infection in a subject in need thereof comprisingadministering an effective amount of the compound to the subject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof for treating or ameliorating abacterial infection resulting from a bacteria that is a Gram-negative orGram-positive type in a subject in need thereof comprising administeringan effective amount of the compound to the subject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof for treating or ameliorating abacterial infection resulting from a bacteria that is a resistantGram-negative or Gram-positive type in a subject in need thereofcomprising administering an effective amount of the compound to thesubject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof in the manufacture of a medicament fortreating or ameliorating a bacterial infection in a subject in needthereof comprising administering an effective amount of the medicamentto the subject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof in the manufacture of a medicament fortreating or ameliorating a bacterial infection resulting from a bacteriathat is a Gram-negative or Gram-positive type in a subject in needthereof comprising administering an effective amount of the compound tothe subject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof in the manufacture of a medicament fortreating or ameliorating a bacterial infection resulting from a bacteriathat is a resistant Gram-negative or Gram-positive type in a subject inneed thereof comprising administering an effective amount of thecompound to the subject.

An embodiment of the present description relates to a use of a compoundof Formula (I) or a form thereof in the preparation of a pharmaceuticalkit comprising the compound of Formula (I) or a form thereof andinstructions for administering the compound for treating or amelioratinga bacterial infection in a subject in need thereof.

Another embodiment of the present description relates to the use of acompound of Formula (I) or a form thereof for treating or ameliorating abacterial infection by selectively inhibiting DNA gyrase andtopoisomerase IV compared to human topoisomerase II.

An embodiment of the present description relates to a method of treatingor ameliorating a bacterial infection or disorders or symptomsassociated therewith in a subject in need thereof comprisingadministering an effective amount of a compound of Formula (I) or a formthereof to the subject.

An embodiment of the present description relates to the use of acompound of Formula (I) or a form thereof in the manufacture of amedicament for treating or ameliorating bacterial infection or disordersor symptoms associated therewith in a subject in need thereof comprisingadministering an effective amount of the medicament to the subject.

An embodiment of the present description relates to the use of acompound of Formula (I) or a form thereof in the preparation of apharmaceutical kit comprising the compound of Formula (I) or a formthereof and instructions for administering the compound for treating orameliorating a bacterial infection or disorders or symptoms associatedtherewith in a subject in need thereof.

In one respect, for each of such embodiments, the subject is treatmentnaive. In another respect, for each of such embodiments, the subject isnot treatment naive.

As used herein, the term “treating” refers to: (i) preventing a disease,disorder or condition from occurring in a subject that may bepredisposed to the disease, disorder and/or condition but has not yetbeen diagnosed as having the disease, disorder and/or condition; (ii)inhibiting a disease, disorder or condition, i.e., arresting thedevelopment thereof; and/or (iii) relieving a disease, disorder orcondition, i.e., causing regression of the disease, disorder and/orcondition.

As used herein, the term “subject” refers to an animal or any livingorganism having sensation and the power of voluntary movement, and whichrequires oxygen and organic food. Nonlimiting examples include membersof the human, equine, porcine, bovine, murine, canine and feline specie.In some embodiments, the subject is a mammal or a warm-bloodedvertebrate animal. In other embodiments, the subject is a human. As usedherein, the term “patient” may be used interchangeably with “subject”and “human”.

Another aspect of the description relates to a method of treating orameliorating a bacterial infection resulting from a bacteria that is aGram-negative or Gram-positive type.

Another aspect of the description relates to a method of treating orameliorating a bacterial infection resulting from bacteria that is aresistant Gram-negative or Gram-positive type.

Another aspect of the description particularly relates to a method oftreating or ameliorating a bacterial infection by a wild type bacteriathat is resistant to a currently available antibacterial agent, in asubject in need thereof, comprising administering to the subject aneffective amount of a compound of Formula (I) or a form thereof.

Examples of bacterial infections intended to be included within thescope of the description include bacterial infections resulting from abacteria of the phyla including, but not limited to, Acidobacteria;Actinobacteria; Aquificae; Bacteroidetes; Caldiserica; Chlamydiae;Chlorobi; Chloroflexi; Chrysiogenetes; Cyanobacteria; Deferribacteres;Deinococcus-Thermus; Dictyoglomi; Elusimicrobia; Fibrobacteres;Firmicutes; Fusobacteria; Gemmatimonadetes; Lentisphaerae; Nitrospira;Planctomycetes; Proteobacteria; Spirochaetes; Synergistetes;Tenericutes; Firmicutes; Thermodesulfobacteria; Thermomicrobia;Thermotogae; or Verrucomicrobia. The listing of phyla is obtained fromthe List of Prokaryotic Names with Standing in Nomenclature (LPSN) (see,http://www.bacterio.cict.fr/index.html)

Another aspect of the description relates to a method of treating orameliorating a bacterial infection by a bacteria from a phyla that is aGram-negative or Gram-positive type.

Another aspect of the description relates to a method of treating orameliorating a bacterial infection by a bacteria from a phyla that is adrug resistant Gram-negative or Gram-positive type.

Another aspect of the description relates to a method of treating orameliorating a bacterial infection by a bacteria from a phyla that is amulti-drug resistant Gram-negative or Gram-positive type.

Examples of such bacterial infections intended to be included within thescope of the description particularly include bacterial infections thatresult from a bacteria of the phyla selected from Proteobacteria,Spirochaetes, Bacteriodetes, Chlamydiae, Firmicutes or Actinobacteria.

In a particular example, the bacterial infections include thoseresulting from a bacterial species selected from Acinetobacterbaumannii, Bacillus anthracis, Bacillus subtilis, Enterobacter spp.,Enterococcus faecalis, Enterococcus faecalis, Enterococcus faecium,Escherichia coli, Francisella tularensis, Haemophilus influenzae,Klebsiella pneumoniae, Moraxella catarrhalis, Mycobacteriumtuberculosis, Neisseria spp., Pseudomonas aeruginosa, Shigella spp.,Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniaeand Yersinia pestis.

In another particular example, the bacteria are selected fromAcinetobacter baumannii BAA747, Acinetobacter baumannii MMX2240 (MDR),Bacillus anthracis (wild-type), Bacillus anthracis T105-R (Cipro^(R)),Bacillus subtilis 23857, Enterococcus faecalis 29212, Enterococcusfaecalis 44841 (quin^(R)), Enterococcus faecium 49624, Escherichia coliBAS849, Escherichia coli 25922, Escherichia coli LZ3111, Escherichiacoli LZ3110, Escherichia coli ELZ4251 (MDR), Escherichia coli NDM-1,Francisella tularensis (wild-type), Haemophilus influenzae 49247,Klebsiella pneumoniae 35657, Klebsiella pneumoniae MMX1232 (MDR),Moraxella catarrhalis 25238, Pseudomonas aeruginosa 27853,Staphylococcus aureus 29213, Staphylococcus aureus 43300 (MDR),Staphylococcus aureus 700789 (MDR), Streptococcus pneumoniae 49150 orYersinia pestis (wild-type).

Another aspect of the description relates to a method of treating orameliorating treating a bacterial infection by a Gram-negative orGram-positive bacteria.

Another aspect of the description relates to a method of treating orameliorating treating a bacterial infection by a resistant Gram-negativeor Gram-positive bacteria.

Another aspect of the description relates to a method of treating orameliorating treating a bacterial infection by a drug resistantGram-negative or Gram-positive bacteria.

Another aspect of the description relates to a method of treating orameliorating treating a bacterial infection by a multi-drug resistantGram-negative or Gram-positive bacteria.

As used herein, the terms “effective amount” or “therapeuticallyeffective amount” mean an amount of compound of Formula (I) or a form,composition or medicament thereof effective in inhibiting theabove-noted diseases and thus producing the desired therapeutic,ameliorative, inhibitory or preventative effect in a subject in needthereof.

In general, the effective amount will be in a range of from about 0.001mg/Kg/day to about 500 mg/Kg/day, or about 0.01 mg/Kg/day to about 500mg/Kg/day, or about 0.1 mg to about 500 mg/Kg/day, or about 1.0 mg/dayto about 500 mg/Kg/day, in single, divided, or a continuous dose for apatient or subject having a weight in a range of between about 40 toabout 200 Kg (which dose may be adjusted for patients or subjects aboveor below this range, particularly children under 40 Kg). The typicaladult subject is expected to have a median weight in a range of betweenabout 60 to about 100 Kg.

The dose administered to achieve an effective target plasmaconcentration may also be administered based upon the weight of thesubject or patient. Doses administered on a weight basis may be in therange of about 0.01 mg/kg/day to about 50 mg/kg/day, or about 0.015mg/kg/day to about 20 mg/kg/day, or about 0.02 mg/kg/day to about 10mg/kg/day, or about 0.025 mg/kg/day to about 10 mg/kg/day, or about 0.03mg/kg/day to about 10 mg/kg/day, wherein said amount is orallyadministered once (once in approximately a 24 hour period), twice (oncein approximately a 12 hour period) or thrice (once in approximately an 8hour period) daily according to subject weight.

In another embodiment, where daily doses are adjusted based upon theweight of the subject or patient, compounds described herein may beformulated for delivery at about 0.02, 0.025, 0.03, 0.05, 0.06, 0.075,0.08, 0.09, 0.10, 0.20, 0.25, 0.30, 0.50, 0.60, 0.75, 0.80, 0.90, 1.0,1.10, 1.20, 1.25, 1.50, 1.75, 2.0, 5.0, 10, 20 or 50 mg/kg/day. Dailydoses adjusted based upon the weight of the subject or patient may beadministered as a single, divided, or continuous dose. In embodimentswhere a dose of compound is given more than once per day, the dose maybe administered twice, thrice, or more per day.

Within the scope of the present description, the “effective amount” of acompound of Formula (I) or a form thereof for use and for use in themanufacture of a medicament, the preparation of a pharmaceutical kit orin a method of treating or ameliorating bacterial infection or disordersor symptoms associated therewith in a subject in need thereof, isintended to include an amount in a range of from about 1.0 mg to about3500 mg administered once daily; 10.0 mg to about 600 mg administeredonce daily; 0.5 mg to about 2000 mg administered twice daily; or, anamount in a range of from about 5.0 mg to about 300 mg administeredtwice daily.

For example, the effective amount may be the amount required to treat abacterial infection, or the amount required to inhibit bacterialreplication in a subject or, more specifically, in a human. In someinstances, the desired effect can be determined by analyzing thepresence of bacterial DNA. The effective amount for a subject willdepend upon various factors, including the subject's body weight, sizeand health. Effective amounts for a given patient can be determined byroutine experimentation that is within the skill and judgment of theclinician.

For any compound, the effective amount can be estimated initially eitherin cell culture assays or in relevant animal models, such as a mouse,chimpanzee, marmoset or tamarin animal model. Relevant animal models mayalso be used to determine the appropriate concentration range and routeof administration. Such information can then be used to determine usefuldoses and routes for administration in humans. Therapeutic efficacy andtoxicity may be determined by standard pharmaceutical procedures in cellcultures or experimental animals, e.g., ED₅₀ (the dose therapeuticallyeffective in 50% of the population) and LD₅₀ (the dose lethal to 50% ofthe population). The dose ratio between therapeutic and toxic effects isreferred to as the therapeutic index, and can be expressed as the ratio,LD₅₀/ED₅₀. In some embodiments, the effective amount is such that alarge therapeutic index is achieved. In further embodiments, the dosageis within a range of circulating concentrations that include an ED₅₀with little or no toxicity. The dosage may vary within this rangedepending upon the dosage form employed, sensitivity of the patient, andthe route of administration.

More specifically, the concentration-biological effect relationshipsobserved with regard to a compound of Formula (I) or a form thereofindicate a target plasma concentration ranging from approximately 0.001μg/mL to approximately 50 μg/mL, from approximately 0.01 μg/mL toapproximately 20 μg/mL, from approximately 0.05 μg/mL to approximately10 μg/mL, or from approximately 0.1 μg/mL to approximately 5 μg/mL. Toachieve such plasma concentrations, the compounds described herein maybe administered at doses that vary from 0.1 μg to 100,000 mg, dependingupon the route of administration in single, divided, or continuous dosesfor a patient weighing between about 40 to about 100 kg (which dose maybe adjusted for patients above or below this weight range, particularlychildren under 40 kg).

The exact dosage will be determined by the practitioner, in light offactors related to the subject. Dosage and administration may beadjusted to provide sufficient levels of the active agent(s) or tomaintain the desired effect. Factors which may be taken into accountinclude the severity of the disease state, general health of thesubject, ethnicity, age, weight, and gender of the subject, diet, timeand frequency of administration, drug combination(s), reactionsensitivities, experience with other antibacterial therapies, andtolerance/response to therapy. Long-acting pharmaceutical compositionsmay be administered every 2, 3 or 4 days, once every week, or once everytwo weeks depending on half-life and clearance rate of the particularformulation.

The compounds and compositions described herein may be administered tothe subject via any drug delivery route known in the art. Nonlimitingexamples include oral, ocular, rectal, buccal, topical, nasal,ophthalmic, subcutaneous, intramuscular, intraveneous (bolus andinfusion), intracerebral, transdermal, and pulmonary routes ofadministration.

Metabolites of the Compounds

Also falling within the scope of the present description are the in vivometabolic products of the compounds described herein. Such products mayresult, for example, from the oxidation, reduction, hydrolysis,amidation, esterification and the like of the administered compound,primarily due to enzymatic processes. Accordingly, the descriptionincludes compounds produced by a process comprising contacting acompound described herein with a mammalian tissue or a mammal for aperiod of time sufficient to yield a metabolic product thereof.

Such products typically are identified by preparing a radio-labeledisotopologue (e.g., C¹⁴ or H³) of a compound described herein,administering the radio-labeled compound in a detectable dose (e.g.,greater than about 0.5 mg/kg) to a mammal such as a rat, mouse, guineapig, dog, monkey or human, allowing sufficient time for metabolism tooccur (typically about 30 seconds to about 30 hours), and identifyingthe metabolic conversion products from urine, bile, blood or otherbiological samples. These products are easily isolated since they are“radiolabeled” by virtue of being isotopically-enriched (others areisolated by the use of antibodies capable of binding epitopes survivingin the metabolite). The metabolite structures are determined inconventional fashion, e.g., by MS or NMR analysis. In general, analysisof metabolites may be done in the same way as conventional drugmetabolism studies well-known to those skilled in the art. Theconversion products, so long as they are not otherwise found in vivo,are useful in diagnostic assays for therapeutic dosing of the compoundsdescribed herein even if they possess no biological activity of theirown.

Pharmaceutical Compositions

Embodiments of the present description include the use of a compound ofFormula (I) or a form thereof in a pharmaceutical composition for theprevention or treatment of a bacterial infection comprising an effectiveamount of a compound of Formula (I) or a form thereof in admixture witha pharmaceutically acceptable excipient.

As used herein, the term “composition” means a product comprising thespecified ingredients in the specified amounts, as well as any productwhich results, directly or indirectly, from combination of the specifiedingredients in the specified amounts.

The pharmaceutical composition may be formulated to achieve aphysiologically compatible pH, ranging from about pH 3 to about pH 11.In some embodiments, the pharmaceutical composition is formulated toachieve a pH of from about pH 3 to about pH 7. In other embodiments, thepharmaceutical composition is formulated to achieve a pH of from aboutpH 5 to about pH 8.

The term “pharmaceutically acceptable excipient” refers to an excipientfor administration of a pharmaceutical agent, such as the compoundsdescribed herein. The term refers to any pharmaceutical excipient thatmay be administered without undue toxicity. Pharmaceutically acceptableexcipients may be determined in part by the particular composition beingadministered, as well as by the particular mode of administration and/ordosage form. Nonlimiting examples of pharmaceutically acceptableexcipients include carriers, solvents, stabilizers, adjuvants, diluents,etc. Accordingly, there exists a wide variety of suitable formulationsof pharmaceutical compositions for the instant compoounds describedherein (see, e.g., Remington's Pharmaceutical Sciences).

Suitable excipients may be carrier molecules that include large, slowlymetabolized macromolecules such as proteins, polysaccharides, polylacticacids, polyglycolic acids, polymeric amino acids, amino acid copolymers,and inactive antibodies. Other exemplary excipients include antioxidantssuch as ascorbic acid; chelating agents such as EDTA; carbohydrates suchas dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearicacid; liquids such as oils, water, saline, glycerol and ethanol; wettingor emulsifying agents; pH buffering substances; and the like. Liposomesare also included within the definition of pharmaceutically acceptableexcipients.

The pharmaceutical compositions described herein may be formulated inany form suitable for the intended method of administration. Suitableformulations for oral administration include solids, liquid solutions,emulsions and suspensions, while suitable inhaleable formulations forpulmonary administration include liquids and powders. Alternativeformulations include syrups, creams, ointments, tablets, and lyophilizedsolids which can be reconstituted with a physiologically compatiblesolvent prior to administration.

When intended for oral use for example, tablets, troches, lozenges,aqueous or oil suspensions, non-aqueous solutions, dispersible powdersor granules (including micronized particles or nanoparticles),emulsions, hard or soft capsules, syrups or elixirs may be prepared.Compositions intended for oral use may be prepared according to anymethod known to the art for the manufacture of pharmaceuticalcompositions, and such compositions may contain one or more agentsincluding sweetening agents, flavoring agents, coloring agents andpreserving agents, in order to provide a palatable preparation.

Pharmaceutically acceptable excipients suitable for use in conjunctionwith tablets include, for example, inert diluents, such as celluloses,calcium or sodium carbonate, lactose, calcium or sodium phosphate;disintegrating agents, such as croscarmellose sodium, cross-linkedpovidone, maize starch, or alginic acid; binding agents, such aspovidone, starch, gelatin or acacia; and lubricating agents, such asmagnesium stearate, stearic acid or talc. Tablets may be uncoated or maybe coated by known techniques including microencapsulation to delaydisintegration and adsorption in the gastrointestinal tract and therebyprovide a sustained action over a longer period. For example, a timedelay material such as glyceryl monostearate or glyceryl distearatealone or with a wax may be employed.

Formulations for oral use may be also presented as hard gelatin capsuleswhere the active ingredient is mixed with an inert solid diluent, forexample celluloses, lactose, calcium phosphate or kaolin, or as softgelatin capsules wherein the active ingredient is mixed with non-aqueousor oil medium, such as glycerin, propylene glycol, polyethylene glycol,peanut oil, liquid paraffin or olive oil.

In other embodiments, pharmaceutical compositions described herein maybe formulated as suspensions comprising a compound of Formula (I) or aform thereof in admixture with at least one pharmaceutically acceptableexcipient suitable for the manufacture of a suspension. In yet otherembodiments, pharmaceutical compositions described herein may beformulated as dispersible powders and granules suitable for preparationof a suspension by the addition of one or more excipient(s).

Excipients suitable for use in connection with suspensions includesuspending agents, such as sodium carboxymethylcellulose,methylcellulose, hydroxypropyl methylcelluose, sodium alginate,polyvinylpyrrolidone, gum tragacanth, gum acacia, dispersing or wettingagents such as a naturally occurring phosphatide (e.g., lecithin), acondensation product of an alkylene oxide with a fatty acid (e.g.,polyoxyethylene stearate), a condensation product of ethylene oxide witha long chain aliphatic alcohol (e.g., heptadecaethyleneoxycethanol), acondensation product of ethylene oxide with a partial ester derived froma fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitanmonooleate); and thickening agents, such as carbomer, beeswax, hardparaffin or cetyl alcohol. The suspensions may also contain one or morepreservatives such as acetic acid, methyl and/or n-propylp-hydroxy-benzoate; one or more coloring agents; one or more flavoringagents; and one or more sweetening agents such as sucrose or saccharin.

The pharmaceutical compositions described herein may also be in the formof oil-in-water emulsions. The oily phase may be a vegetable oil, suchas olive oil or arachis oil, a mineral oil, such as liquid paraffin, ora mixture of these. Suitable emulsifying agents includenaturally-occurring gums, such as gum acacia and gum tragacanth;naturally occurring phosphatides, such as soybean lecithin, esters orpartial esters derived from fatty acids; hexitol anhydrides, such assorbitan monooleate; and condensation products of these partial esterswith ethylene oxide, such as polyoxyethylene sorbitan monooleate. Theemulsion may also contain sweetening and flavoring agents. Syrups andelixirs may be formulated with sweetening agents, such as glycerol,sorbitol or sucrose. Such formulations may also contain a demulcent, apreservative, a flavoring or a coloring agent.

Additionally, the pharmaceutical compositions described herein may be inthe form of a sterile injectable preparation, such as a sterileinjectable aqueous emulsion or oleaginous suspension. Such emulsion orsuspension may be formulated according to the known art using thosesuitable dispersing or wetting agents and suspending agents which havebeen mentioned above. The sterile injectable preparation may also be asterile injectable solution or suspension in a non-toxic parenterallyacceptable diluent or solvent. The sterile injectable preparation mayalso be prepared as a lyophilized powder. Among the acceptable vehiclesand solvents that may be employed are water, Ringer's solution, andisotonic sodium chloride solution. In addition, sterile fixed oils maybe employed as a solvent or suspending medium. For this purpose anybland fixed oil may be employed including synthetic mono- ordi-glycerides. In addition, fatty acids such as oleic acid may likewisebe used in the preparation of injectables.

The compounds described herein may be substantially insoluble in waterand sparingly soluble in most pharmaceutically acceptable proticsolvents and vegetable oils, but generally soluble in medium-chain fattyacids (e.g., caprylic and capric acids) or triglycerides and inpropylene glycol esters of medium-chain fatty acids. Thus, contemplatedin the description are compounds which have been modified bysubstitutions or additions of chemical or biochemical moieties whichmake them more suitable for delivery (e.g., increase solubility,bioactivity, palatability, decrease adverse reactions, etc.), forexample by esterification, glycosylation, PEGylation, etc.

In some embodiments, the compound described herein is formulated fororal administration in a lipid-based composition suitable for lowsolubility compounds. Lipid-based formulations can generally enhance theoral bioavailability of such compounds. As such, pharmaceuticalcompositions described herein may comprise a effective amount of acompound of Formula (I) or a form thereof, together with at least onepharmaceutically acceptable excipient selected from medium chain fattyacids or propylene glycol esters thereof (e.g., propylene glycol estersof edible fatty acids such as caprylic and capric fatty acids) andpharmaceutically acceptable surfactants, such as polyoxyl 40hydrogenated castor oil.

In other embodiments, the bioavailability of low solubility compoundsmay be enhanced using particle size optimization techniques includingthe preparation of nanoparticles or nanosuspensions using techniquesknown to those skilled in art. The compound forms present in suchpreparations include amorphous, partially amorphous, partiallycrystalline or crystalline forms.

In alternative embodiments, the pharmaceutical composition may furthercomprise one or more aqueous solubility enhancer(s), such as acyclodextrin. Nonlimiting examples of cyclodextrin includehydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosylderivatives of α-, β-, and γ-cyclodextrin, andhydroxypropyl-β-cyclodextrin (HPBC). In some embodiments, thepharmaceutical composition further comprises HPBC in a range of fromabout 0.1% to about 20%, from about 1% to about 15%, or from about 2.5%to about 10%. The amount of solubility enhancer employed may depend onthe amount of the compound in the composition.

Preparation of Compounds General Synthetic Examples

Methods for preparing certain compounds useful for treating orameliorating bacterial infections or disorders or symptoms associatedtherewith are available via standard, well-known syntheticmethodologies.

As disclosed herein, methods for preparing the compounds describedherein are also available via standard, well-known syntheticmethodology. Many of the starting materials used herein are commerciallyavailable or can be prepared using the routes described below usingtechniques known to those skilled in the art.

General Schemes

Compounds of Formula (I) can be prepared as described in the Schemesbelow.

General Procedures for Scheme 1

Ketones of type 1C (wherein R represents one or more optionally presentsubstituents or protecting groups) are prepared from carboxylic acids oftype 1A by a two step procedure beginning with treatment of carboxylicacids of type 1A with an appropriate activating agent followed byreaction with N,O-dimethylhydroxylamine in an organic solvent (such asDCM and the like). Ketones of type 1C may then be prepared from amidesof type 1B by reaction with an aryl metallated species where the metalis lithium or magnesium and the like.

General Procedure for Scheme 2

The ketone moiety starting materials used in Scheme 2 were prepared viathe procedures described in Scheme 1. An alternative procedure toprepare ketones of type 1C includes reacting aryl nitriles of type 2A(wherein R represents one or more optionally present substituents orprotecting groups) with Grignard reagents in a suitable organic solvent(such as THF and the like) followed by treatment with an aqueous acid.

General Procedures for Scheme 3

A ketone of type 1C may be converted into an imine of type 3A (wherein Rrepresents one or more optionally present substituents or protectinggroups) by reaction with an excess of tert-butyl amine in the presenceof a Lewis acid (such as titanium tetrachloride and the like) ordehydrating agents (such as para-toluene sulfonic acid and the like) inan organic solvent (such as DCM and the like). Imines of type 3A may beused to obtain 2-pyridones of type 3B by reaction with dimethyl2-(methoxymethylene)malonate in a solvent (such as diphenyl ether andthe like) at temperatures ranging from 130° C. to 230° C. The estermoiety on the pyridone of type 3B may be converted to the correspondingcarboxylic acid of type 3C by reaction with aqueous lithium hydroxide inan organic solvent (such as THF and the like) at 50° C.

General Procedure for Scheme 4

Imines of type 3A may also be used to obtain hydroxyl 2-pyridones oftype 4A by reaction with a trialkyl tricarboxylate in a solvent (such asdiphenyl ether and the like) at temperatures ranging from 130° C. to230° C. Hydrolysis of the ester moiety on the hydroxy 2-pyridone of type4A is achieved with aqueous hydroxide in a suitable organic solvent(such as THF and the like) or by reaction with iodotrimethyl silane orlithium iodide in an organic solvent (such as EtOAc and the like) attemperatures ranging from 30° C. to 80° C. to provide hydroxyl2-pyridones of type 4B.

General Procedure for Scheme 5

Anilines of type 5B (wherein R represents one or more optionally presentsubstituents or protecting groups and, wherein the amine R groups can betaken together with the nitrogen of attachment to form a heterocyclylring) are prepared from aryl halides of type 5A (wherein X representsone or more optionally present substituents or protecting or leavinggroups) by treatment with an amine, a suitable base, and a suitablepalladium catalyst in an appropriate organic solvent at temperaturesranging from 80° C. to 110° C. followed by hydrolysis of the estermoiety on the 5B intermediate to provide the corresponding carboxylicacid of type 5B.

General Procedure for Scheme 6

Ketones of type 6A (wherein X represents one or more optionally presentsubstituents or protecting or leaving groups) may be used to prepareimines of type 6B by reaction with an excess of dimethoxybenzyl amine inthe presence of a dehydrating agent (such as para-toluene sulfonic acidand the like) or a Lewis acid (such as titanium tetrachloride and thelike) in an organic solvent (such as DCM and the like). Imines of type6B may be used to obtain 2-pyridones of type 6C (wherein R representsone or more optionally present substituents or protecting groups) byreaction with dialkyl 2-(alkoxymethylene)malonate in an organic solvent(such as diphenyl ether and the like) at temperatures ranging from 130°C. to 230° C.

General Procedure for Scheme 7

Aryl halides of type 6C may be used to obtain anilines of type 7A(wherein R represents one or more optionally present substituents orprotecting groups and, wherein the amine R groups can be taken togetherwith the nitrogen of attachment to form a heterocyclyl ring) bytreatment with an amine, a suitable base, and a suitable palladiumcatalyst in an appropriate organic solvent at temperatures ranging from80° C. to 110° C., followed by hydroysis of the ester moiety on the 6Cintermediate to provide the corresponding carboxylic acid of type 7A.2-Pyridones of type 7C are prepared by treatment of the aniline of type7A with an acid such as trifluoroacetic acid in a suitable organicsolvent (such as DCM and the like).

General Procedure for Scheme 8

A ketone of type 6A may be used to obtain an imine of type 8A byreaction with an excess of tertbutyl amine in the presence of adehydrating agent (such as para-toluene sulfonic acid and the like) or aLewis acid (such as titanium tetrachloride and the like) in an organicsolvent (such as DCM and the like). Imines of type 8A may be used toobtain 2-pyridones of type 8B (wherein R represents one or moreoptionally present substituents or protecting groups) by reaction withtrialkyl methane tricarboxylate in an organic solvent (such as diphenylether and the like) at temperatures ranging from 130° C. to 230° C.Pyridines of type 8C are prepared by treatment of the 2-pyridones oftype 8B with benzyl alcohol in the presence of a trialkyl phosphine anddiisopropyl azodicarboxlate in a suitable organic solvent (such as THFand the like).

General Procedure for Scheme 9

The ester moiety on pyridines of type 8C may be hydrolyzed with anappropriate base in a suitable organic solvent (such as THF and thelike) to provide the carboxylic acid substituted aryl halides of type 9AAnilines of type 9B may be prepared from the aryl halides of type 9A bytreatment with an amine, a suitable base, and a suitable palladiumcatalyst in an appropriate organic solvent at temperatures ranging from80° C. to 110° C. Finally, 2-pyridones of type 9C may be accessed frompyridines of type 9B by treatment with hydrogen (H₂) gas in the presenceof a palladium catalyst in an appropriate organic solvent (such as MeOHand the like).

General Procedure for Scheme 10

Aryl and heteroaryl bromides of type 10A may be converted into thecorresponding aryl and heteroaryl boronic esters of type 10B in thepresence of an excess of bis(pinacolato)diboron, a suitable base (suchas potassium acetate and the like) and a suitable palladium catalyst(such as PdCl₂(dppf) and the like) in an organic solvent (such as1,4-dioxane and the like) at temperatures ranging from 80° C. to 110° C.The 2,4-bisbenzyloxypyridines of type 10D are prepared bySuzuki-coupling between heteroaryl boronic esters of type 10B and6-chloro-2,4-bisbenzyloxypyridines of type 10C in the presence of asuitable base (such as potassium carbonate and the like), a suitableligand (such as tri-tert-butylphosphonium tetrafluoroborate and thelike) and a suitable palladium catalyst (such as Pd₂(dba)₃ and the like)in an organic solvent (such as DMSO and the like) at temperaturesranging from 90° C. to 120° C. The 4-hydroxy-2-pyridones of type 10E areprepared by hydrogenolysis of 2,4-bisbenzyloxypyridines of type 10D witha suitable catalyst (such as palladium on carbon and the like) underhydrogen at room temperature.

Specific Examples

To assist in understanding the present description, the followingExamples are included. The experiments relating to this descriptionshould not, of course, be construed as specifically limiting thedescription and such variations of the description, now known or laterdeveloped, which would be within the purview of one skilled in the artare considered to fall within the scope of the description as describedherein and hereinafter claimed.

Other than in the working examples, unless indicated to the contrary,all numbers expressing quantities of ingredients, reaction conditions,experimental data, and so forth used in the specification and claims areto be understood as being modified by the term “about”. Accordingly, allsuch numbers represent approximations that may vary depending upon thedesired properties sought to be obtained by a reaction or as a result ofvariable experimental conditions. Therefore, within an expected range ofexperimental reproducibility, the term “about” in the context of theresulting data, refers to a range for data provided that may varyaccording to a standard deviation from the mean. As well, forexperimental results provided, the resulting data may be rounded up ordown to present data consistently, without loss of significant figures.At the very least, and not as an attempt to limit the application of thedoctrine of equivalents to the scope of the claims, each numericalparameter should be construed in light of the number of significantdigits and ordinary rounding techniques.

While the numerical ranges and parameters setting forth the broad scopeof the description are approximations, the numerical values set forth inthe working examples are reported as precisely as possible. Anynumerical value, however, inherently contains certain errors necessarilyresulting from the standard deviation found in their respective testingmeasurements.

Synthetic Examples

Greater details of the present description are provided with referenceto the following non-limiting examples, which are offered to more fullyillustrate the description, but are not to be construed as limiting thescope thereof. The examples illustrate the preparation of certaincompounds described herein, and the testing of these compounds in vitroand/or in vivo. Those of skill in the art will understand that thetechniques described in these examples represent techniques described bypersons of ordinary skill in the art to function well in the practice ofthe description, and as such constitute preferred modes for the practicethereof. However, those of skill in the art should appreciate in lightof the present disclosure that many changes can be made to the specificmethods that are disclosed and still obtain a like or similar resultwithout departing from the spirit and scope of the description. Forexample, various conditions were used to obtain LC-MS characterizationfor the compounds described herein.

As indicated for certain compounds, the 2 Minute Method uses thefollowing column and mobile phase ratios:

Column: Acquity UPLC HSS C18 Column 2.1 × 50 mm, 1.8 μm Mobile Phase A:H₂O/0.1% HCO₂H Mobile Phase B: Acetonitrile/0.1% HCO₂H Time (min) Flow(mL/min) % A % B 1 0 0.8 100 0 2 0.2 0.8 100 0 3 1.5 0.8 0 100 4 2.0 0.8100 0

As indicated for certain compounds, the 1 Minute Method uses thefollowing column and mobile phase ratios:

Column: Acquity UPLC HSS C18 Column 2.1 × 50 mm, 1.8 μm Mobile Phase A:H₂O/0.1% HCO₂H Mobile Phase B: Acetonitrile/0.1% HCO₂H Time (min) Flow(mL/min) % A % B 1 0 0.8 90 10 2 0.1 0.8 90 10 3 0.8 0.8 5 95 4 1.0 0.890 10

As indicated for certain compounds, the Polar Method uses the followingcolumn and mobile phase ratios:

Column: Acquity UPLC HSS C18 Column 2.1 × 50 mm, 1.8 μm Mobile Phase A:H₂O/0.1% HCO₂H Mobile Phase B: Acetonitrile/0.1% HCO₂H Time (min) Flow(mL/min) % A % B 1 0 0.8 100 0 2 0.2 0.8 100 0 3 1.5 0.8 50 50 4 2.0 0.8100 0

As indicated for certain compounds, Method A uses the following columnand mobile phase ratios:

Column: HSS T3 Column 2.1 × 50 mm, 1.8 μm Mobile Phase A: H₂O/0.1% HCO₂HMobile Phase B: Acetonitrile/0.1% HCO₂H Time (min) Flow (ml/min) % A % B1 0 0.8 80 20 2 0.2 0.8 80 20 3 1.25 0.8 5 95 4 2.0 0.8 80 20

As indicated for certain compounds, Method B uses the following columnand mobile phase ratios:

Column: HSS T3 Column 2.1 × 50 mm, 1.8 μm Mobile Phase A: H₂O/0.1% HCO₂HMobile Phase B: Acetonitrile/0.1% HCO₂H Time (min) Flow (ml/min) % A % B1 0 0.8 95 5 2 0.2 0.8 95 5 3 1.5 0.8 10 90 4 2.0 0.8 95 5

As indicated for certain compounds, Method C uses the following columnand mobile phase ratios:

Column: BEH C18 Column 2.1 × 50 mm, 1.7 μm Mobile Phase A: NH₄OAc_(aq)10 mM Mobile Phase B: Acetonitrile Time (min) Flow (ml/min) % A % B 1 00.8 95 5 2 0.2 0.8 95 5 3 1.5 0.8 10 90 4 2.0 0.8 95 5

As used above, and throughout this description, the followingabbreviations, unless otherwise indicated, shall be understood to havethe following meanings:

Abbreviation Meaning AcOH or HOAc acetic acid ACN or MeCN acetonitrileatm atmosphere Bn benzyl BnBr benzyl bromide BnO or OBn benzyloxy BnOHbenzyl alcohol DCM dichloromethane (CH₂Cl₂) DIAD diisopropylazodicarboxylate DMF dimethylformamide DMA dimethylacetamide DMBdimethoxybenzyl DMSO dimethylsulfoxide EtOAc ethyl acetate EtOH ethanolEt₂O diethyl ether HPLC high performance liquid chromatography KFpotassium fluoride KOAc potassium acetate h/hr/min/s hour(h orhr)/minute(min)/second(s) LC/MS, LCMS or LC-MS liquid chromatographicmass spectroscopy LDA lithium diisopropylamine LiOH lithium hydroxideMeI methyl iodide MeOH methanol Me₂NH N-methylmethanamine MS massspectroscopy NaBH(OAc)₃ sodium triacetoxyborohydride NMON-methylmorpholine-N-oxide n-Bu n-butyl n-BuLi n-butyl lithium NMRnuclear magnetic resonance nPr or n-Pr n-propyl OSO₄ osmium tetroxidePd° palladium Pd₂(dba)₃ tris(dibenzylideneacetone)dipalladium(0)PdCl₂(dppf) [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II)Pd(OAc)₂ palladium acetate Pd(PPb₃)₄tetrakis(triphenylphosphine)palladium Ph₂O diphenyl ether PPh₃triphenylphosphine psi pounds per square inch pressure PTFEpolytetrafluoroethylene RT retention time TEA or NEt₃ triethylamine TPAtrifluoroacetic acid THF tetrahydrofuran THP tetrahydro-2H-pyranyl THPOor OTHP tetrahydro-2H-pyran-2-yloxy TiCl₄ titanium tetrachloride TMSItrimethylsilyl iodide TMSOK potassium trimethylsilanolate

EXAMPLE 15-benzyl-6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 1) Step 1: N-methoxy-N-methyl-3-phenylpropanamide

To a solution of 3-phenylpropanoic acid (6.6 g, 43.9 mmol) and oxalylchloride (4.0 mL, 49 mmol) in CH₂Cl₂ (60 mL) was added DMF (100 μL). Theresulting solution was stirred for 1 hr at room temperature and thenconcentrated. The crude residue was taken up in CH₂Cl₂ (60 mL) thenN,O-dimethylhydroxylamine hydrochloride (4.71 g, 49 mmol) and pyridine(5.3 mL, 65 mmol) were added. After stirring at room temperature for 2hrs, the solution was washed with water (100 mL) and then 1M HCl. Theorganic phase was dried with Na₂SO₄, then filtered and concentrated togive the title compound as a white solid (7.5 g, 38.6 mmol, 88%).

¹H NMR (500 MHz, CDCl₃) δ 2.67 (t, J=7.80 Hz, 2H), 2.86-2.92 (m, 2H),3.11 (s, 3H), 3.54 (s, 3H), 7.10-7.24 (m, 5H).

Step 2: 1-(4-(dimethylamino)phenyl)-3-phenylpropan-1-one

To a solution of N-methoxy-N-methyl-3-phenylpropanamide (4.7 g, 24.3mmol) in tetrahydrofuran (100 mL), cooled to −78° C., was added asolution of (4-(dimethylamino)phenyl)magnesium bromide intetrahydrofuran (50 mL, 0.5M, 25 mmol). After stirring at −78° C. for 30min, the reaction mixture was allowed to warm to room temperature, thenstirred for an additional 1 hr. The reaction was quenched with asaturated solution of ammonium chloride, then poured into water andextracted with ethyl acetate. The combined extracts were dried overNa₂SO₄, then filtered, and concentrated to give the title compound (6.0g, 23.8 mmol, 98%).

¹H NMR (500 MHz, CDCl₃) δ 3.03-3.12 (m, 2H), 3.07 (s, 6H), 3.17-3.26 (m,2H), 6.71 (m, 2H), 7.25-7.34 (m, 5H), 7.94 (m, 2H).

Step 3: 4-(1-(tert-butylimino)-3-phenylpropyl)-N,N-dimethylaniline

To a solution of 1-(4-(dimethylamino)phenyl)-3-phenylpropan-1-one (2.0g, 8.0 mmol) and t-butylamine (3.3 mL, 32 mmol) in DCM (15 mL) was addeda 1M solution of TiCl₄ (5.2 mL, 4.8 mmol) dropwise at 0° C. over 30 minAfter completion of the addition, the reaction mixture was stirred atroom temperature overnight and the reaction was quenched with saturatedaqueous sodium bicarbonate. The product was extracted with DCM and thecombined organic phases were dried over Na₂SO₄, then filtered andconcentrated to give the title compound as a crude product that was usedimmediately without further purification.

Step 4: methyl5-benzyl-6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

A solution of 4-(1-(tert-butylimino)-3-phenylpropyl)-N,N-dimethylaniline(0.53 g, 1.7 mmol) and dimethyl 2-(methoxymethylene)malonate (2.55 g.1.87 mmol) in diglyme (2 mL) was heated at 160° C. for 4 h. The reactionmixture was cooled to room temperature, then the precipitate wasfiltered and washed with diethyl ether to afford the title compound as ayellow solid (0.22 g, 0.61 mmol, 36%).

¹H NMR (500 MHz, DMSO-d₆) δ 2.97 (s, 6H), 3.71 (s, 3H), 3.78 (s, 2H),6.76 (m, 2H), 7.05 (m, 2H), 7.16-7.23 (m, 1H), 7.24-7.32 (m, 4H), 7.88(s, 1H), 11.90 (br. S., 1H).

Step 5:5-benzyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid

A solution of methyl5-benzyl-6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate(125 mg, 0.35 mmol) and aqueous LiOH (2 mL, 1M, 2 mmol) in THF (4 mL)was stirred at 50° C. for 3 hrs. The reaction mixture was allowed tocool to room temperature and then acidified with 1M HCl to pH 4. Theresulting precipitate was filtered and rinsed with diethyl ether toafford the title compound as a yellow solid (88 mg, 0.25 mmol, 72%).

¹H NMR (500 MHz, DMSO-d₆) δ 2.93-3.02 (m, 6H), 3.89 (s, 2H), 6.79 (m,2H), 7.06 (d, 2H), 7.20 (t, 1H), 7.29 (t, 2H), 7.32-7.38 (m, 2H), 8.09(s, 1H). LC-LC-MS 349.3 [M+H]⁺, RT 0.77.

EXAMPLE 25-benzyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 2) Step 1: methyl5-benzyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

A solution of 4-(1-(tert-butylimino)-3-phenylpropyl)-N,N-dimethylaniline(0.52 g, 1.67 mmol) and triethyl methanetricarboxylate (350 μL. 1.84mmol) in diglyme (2 mL) was heated at 160° C. for 4 h. The reactionmixture was cooled to room temperature and the resulting precipitate wasfiltered and washed with diethyl ether to afford the title compound as ayellow solid (0.14 g, 0.36 mmol, 21%).

¹H NMR (500 MHz, DMSO-d₆) δ 1.30 (t, J=7.09 Hz, 3H), 2.94 (s, 6H), 3.72(s, 2H), 4.33 (q, J=7.09 Hz, 2H), 6.71 (m, 2H), 7.05 (m, 2H), 7.18 (m,3H), 7.24 (m, 2H), 11.28-11.35 (s, 1H), 13.58 (s, 1H).

Step 2:5-benzyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid

A solution of methyl5-benzyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(17 mg, 0.04 mmol) and iodotrimethylsilane (20 μL, 0.12 mmol) in amixture of DCM (500 μL) and acetonitrile (500 μL) was stirred at 80° C.for 1.5 hrs. Additional iodotrimethylsilane (20 μL, 0.12 mmol) was addedand the solution was stirred at 80° C. for a further 16 hrs. Thereaction mixture was then cooled to room temperature and the reactionwas quenched with aqueous HCl (1M). The aqueous phase was extracted withDCM (2×20 mL) and the combined organic extracts were dried over Na₂SO₄,then filtered and concentrated to give the title compound (10 mg, 0.03mmol, 69%).

¹H NMR (500 MHz, CDCl₃) δ 2.96 (s, 6H), 3.88 (s, 2H), 6.65 (m, 2H),7.00-7.06 (m, 2H), 7.10-7.23 (m, 5H), 10.78 (br. s, 1H), 13.66 (s, 1H),14.53 (br. s, 1H). LC-MS 365.3 [M+H]⁺, RT 0.86.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 36-(4-aminophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹HNMR (500 MHz, DMSO-d₆) δ ppm 1.06 (t, J = 7.49 Hz, 3H) 2.48 (m, J = 7.50Hz, 2H) 5.73-5.73 (m, 2H) 6.66 (d, J = 8.51 Hz, 2H) 7.17 (d, J = 8.51Hz, 2H) 8.30 (s, 1H) 12.84-13.02 (m, 1H) 14.97-15.06 (m, 1H). 46-[4-(dimethylamino)phenyl]-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CDCl₃) δ 2.21 (s, 3H), 3.01 (s, 6 H), 6.67-6.78(m, 2H), 7.27-7.36 (m, 2H), 8.39 (s, 1H). 56-[4-(dimethylamino)phenyl]-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ 1.97 (s, 3H), 3.00 (s, 6 H),6.74-6.81 (m, 2H), 7.29-7.39 (m, 2H). LC-MS 289.2 [M + H]⁺, RT 0.78. 65-cyclohexyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CDCl₃) δ 1.17 (br s, 4H), 1.37-1.49 (m, 2H),1.60-1.67 (m, 2H), 1.78 (m, 2H), 2.58-2.72 (m, 1H), 3.02 (s, 6 H),6.77-6.79 (m, 2H), 7.19 (s, 3H), 7.26 (s, 2H), 8.48 (s, 1H), 13.73 (s,1H). 75-cyclohexyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CDCl₃) δ 0.92-1.13 (m, 4H), 1.33-1.42(m, 2H), 1.43-1.51 (m, 1H), 1.55-1.63 (m, 2H), 1.95-2.05 (m, 2H),2.85-2.91 (m, 2H), 2.91 (s, 6 H), 6.59-6.64 (m, 2H), 7.04-7.12 (m, 2H),10.35 (s, 1H) 13.85 (s, 1H) 14.67 (s, 1H). 86-[4-(dimethylamino)phenyl]-2-oxo-5-propyl-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ 0.79 (t, J = 1.00 Hz, 2H), 1.41-1.49(m, 2H), 2.43-2.47 (m, 2H), 2.96-3.03 (m, 6 H), 6.75-6.84 (m, 2H),7.30-7.35 (m, 2H), 8.29 (s, 1H), 13.02 (br. s., 1H), 15.05 (br. s, 1H).LC-MS 301.3 [M + H]⁺, RT 0.76. 96-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ 0.71 (t, J = 7.37 Hz, 3H),1.33-1.42 (m, 2H), 2.23-2.32 (m, 2H), 2.93 (s, 6 H), 6.70-6.77 (m, 2H),7.19-7.25 (m, 2H), 13.82 (br s, 1H). 106-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxylic acid ¹HNMR (500 MHz, DMSO-d₆) δ ppm 7.28-7.36 (m, 2H) 7.53-7.60 (m, 2H) 8.05(d, J = 0.63 Hz, 1H) 8.73 (d, J = 0.63 Hz, 1H). LC-MS 278.1 [M + H]⁺, RT0.48. 116-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3,5-dicarboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ 3.02 (s, 6 H), 6.76 (m, 2H), 7.35 (m,1H), 8.63 (s, 1H). LC-MS 303.2 [M + H]⁺, RT 0.52. 125-cyclopropyl-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ 0.51-0.58 (m, 2H), 0.80-0.86 (m, 2H),1.78-1.89 (m, 1H), 3.01 (s, 6 H), 6.82-6.87 (m, 2H), 7.46-7.56 (m, 2H),7.96 (s, 1H), 13.04 (br. s, 1H), 14.99 (br. s., 1H). LC-MS 299.2 [M +H]⁺, RT 0.72. 135-cyclopropyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ 0.45-0.65 (m, 4H), 0.74-0.92(m, 1H), 3.01 (s, 6 H), 6.83 (d, J = 8.9 Hz, 2H), 7.51 (d, J = 8.9 Hz,2H), 12.85-13.26 (m, 1H), 14.86-15.17 (m, 1H). LC-MS 313.2 [M − H]⁻, RT0.80. 145-cyano-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ 3.06 (s, 6 H), 6.80-6.94 (m, 2H),7.58-7.73 (m, 2H), 8.38-8.50 (m, 1H). LC-MS 284.2 [M + H]⁺, RT 0.63. 156-(4-cyanophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹HNMR (500 MHz, DMSO-d₆) δ ppm 1.00 (t, J = 7.53 Hz, 3H) 2.25-2.33 (m, 2H)7.66 (d, J = 6.78 Hz, 2H) 7.94-8.01 (m, 2H) 8.07 (s, 1H). 165-ethyl-6-(4-{methyl[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.12(t, J = 7.4 Hz, 3H) 1.39-1.54 (m, 4H) 1.60-1.67 (m, 1H) 1.68-1.76 (m,1H) 2.54 (q, J = 7.49 Hz, 2H) 3.07 (s, 3H) 3.40-3.47 (m, 1H) 3.56-3.67(m, 3H) 3.74 (ddd, J = 11.23, 8.32, 3.23 Hz, 1H) 3.88-3.95 (m, 1H)4.52-4.59 (m, 1H) 6.90 (d, J = 8.67 Hz, 2H) 7.32 (d, J = 8.91 Hz, 2H)8.43 (s, 1H) 12.36 (br. s., 1H) 13.65 (br. s., 1H). 175-ethyl-6-{4-[(2-hydroxyethyl)(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.09 (t, J = 7.4 Hz 3H)2.45-2.50 (m, 2H) 3.02 (s, 3H) 3.46-3.52 (m, 2H) 3.56-3.61 (m, 2H) 6.85(d, J = 8.83 Hz, 2H) 7.33 (d, J = 8.91 Hz, 2H) 8.31 (s, 1H). 185-ethyl-4-hydroxy-6-{4-[(2-hydroxyethyl)(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.06(t, J = 7.37 Hz, 3H) 2.39 (d, J = 7.41 Hz, 2H) 3.02 (s, 3H) 3.45-3.51(m, 2H) 3.56-3.61 (m, 2H) 6.83 (d, J = 8.91 Hz, 2H) 7.29 (d, J = 8.91Hz, 2H) 12.49-12.57 (m, 1H) 13.82-13.90 (m, 1H). LC-MS 333.3 [M + H]⁺,RT 0.70. 196-[2-(dimethylamino)pyrimidin-5-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.25 (t, J = 7.40 Hz, 3H) 2.61 (q,J = 7.51 Hz, 2H) 3.33 (s, 6 H) 8.50 (s, 2H) 8.57 (s, 1H) 12.60-12.67 (m,1H) 13.30-13.38 (m, 1H). LC-MS 289.3 [M + H]⁺, RT 0.70. 206-[2-(dimethylamino)pyrimidin-5-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.40 Hz,3H) 2.55 (q, J = 7.36 Hz, 2H) 3.34 (s, 6 H) 8.50 (br. s., 2H) 11.56 (br.s., 1H) 13.89 (s, 1H) 14.20 (br. s., 1H). LC-MS 305.3 [M + H]⁺, RT 0.72.214-hydroxy-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.95-2.02 (m, 4H) 3.26-3.37 (m, 4H)6.59 (s, 1H) 6.63 (d, J = 8.91 Hz, 2H) 7.78 (d, J = 8.91 Hz, 2H). LC-MS:301.1 [M + H]⁺, RT 1.25. 225-(aminomethyl)-6-[4-(dimethylamino)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride (1:1) LC-MS: 288.3 [M + H]⁺, RT 0.29. 235-ethyl-2-oxo-6-[4-(1H-tetrazol-5-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.40 Hz, 3H) 2.38-2.45(m, 2H) 7.73-7.78 (m, 2H) 8.18-8.24 (m, 1H) 8.40-8.45 (m, 1H). 245-ethyl-6-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidLC-MS: 274.3 [M + H]⁺, RT 0.96 min. 255-ethyl-4-hydroxy-6-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 290.3 [M + H]⁺, RT 1.16 min. 265-ethyl-6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidLC-MS: 262.3 [M + H]⁺, RT 0.96 min. 275-ethyl-6-(4-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidLC-MS: 259.3 [M + H]⁺, RT 1.01 min. 285-ethyl-4-hydroxy-6-(4-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacidLC-MS: 274.4 [M + H]⁺, RT 1.21 min. 295-ethyl-4-hydroxy-2-oxo-6-[2-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid LC-MS: 343.3 [M + H]⁺, RT 1.21 min. 305-ethyl-6-(2-fluoro-4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 292.2 [M + H]⁺, RT 0.95 min. 315-ethyl-2-oxo-6-[2-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid LC-MS: 327.3 [M + H]⁺, RT 1.07 min. 325-ethyl-4-hydroxy-6-(4-methoxy-2-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 304.2 [M + H]⁺, RT 1.04 min. 335-ethyl-6-(4-methoxy-2-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 288.3 [M + H]⁺, RT 0.92 min. 346-(2,4-dimethoxyphenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 304.3 [M + H]⁺, RT 1.45 min. 355-ethyl-6-[4-methoxy-2-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.3 [M + H]⁺, RT 1.60 min. 366-(2,4-dimethoxyphenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 320.2 [M + H]⁺, RT 1.61 min. 375-ethyl-6-[2-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 327.4 [M + H]⁺, RT 1.64 min. 385-ethyl-6-[2-fluoro-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 331.3 [M + H]⁺, RT 1.59 min. 395-ethyl-4-hydroxy-6-[2-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.3 [M + H]⁺, RT 1.66 min. 406-[2-(dimethylamino)-4-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 317.4 [M + H]⁺, RT 1.83 min. 415-ethyl-4-hydroxy-2-oxo-6-(2,4,6-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid LC-MS: 350.3 [M + H]⁺, RT 1.54 min. 425-ethyl-4-hydroxy-2-oxo-6-(2,3,4-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid LC-MS: 350.4 [M + H]⁺, RT 1.73 min. 435-ethyl-6-[2-fluoro-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 345.2 [M + H]⁺, RT 1.67 min. 445-ethyl-6-[2-fluoro-4-(piperidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 361.2 [M + H]⁺, RT 1.81 min. 455-ethyl-4-hydroxy-6-[2-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 359.4 [M + H]⁺, RT 1.65 min. 465-ethyl-2-oxo-6-[2-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid LC-MS: 313.3 [M + H]⁺, RT 1.55 min. 475-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 329.4 [M + H]⁺, RT 1.73 min. 485-ethyl-4-hydroxy-6-[4-methoxy-2-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 359.4 [M + H]⁺, RT 1.72 min. 495-ethyl-4-hydroxy-6-[2-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 373.4 [M + H]⁺, RT 1.64 min. 505-ethyl-6-[2-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.4 [M + H]⁺, RT 1.57 min. 515-ethyl-4-hydroxy-6-[2-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 357.4 [M + H]⁺, RT 1.72 min. 525-ethyl-6-[2-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 341.4 [M + H]⁺, RT 1.50 min. 536-[4-(dimethylamino)-2-fluorophenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 305.3 [M + H]⁺, RT 1.46 min. 546-[2-(dimethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 287.3 [M + H]⁺, RT 1.52 min. 556-[4-(dimethylamino)-2-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 321.3 [M + H]⁺, RT 1.63 min. 566-[4-(dimethylamino)-2-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyndine-3-carboxylic acid LC-MS: 317.4 [M + H]⁺, RT 1.69 min. 576-[4-(dimethylamino)-2-methylphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 301.3 [M + H]⁺, RT 1.50 min. 586-[2-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 303.3 [M + H]⁺, RT 1.66 min. 595-ethyl-6-[2-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 357.6 [M + H]⁺, RT 1.57 min. 606-[2-(dimethylamino)-4-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 333.5 [M + H]⁺, RT 1.65 min. 616-[4-(dimethylamino)-2-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 333.5[M + H]⁺, RT 1.63 min. 626-[4-(dimethylamino)-2-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 317.6 [M + H]⁺, RT 1.45 min. 636-[4-(dimethylamino)-3-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 317.4 [M + H]⁺, RT 1.62 min. 646-[4-(dimethylamino)-3-methoxyphenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 317.5 [M + H]⁺, RT 1.01 min. 656-[4-(dimethylamino)-3-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 333.3 [M + H]⁺, RT 1.30 min. 665-ethyl-6-[3-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.4 [M + H]⁺, RT 1.49 min. 675-ethyl-4-hydroxy-6-[3-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 359.3 [M + H]⁺, RT 1.72 min. 685-ethyl-6-[3-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 357.4 [M + H]⁺, RT 1.28 min. 695-ethyl-4-hydroxy-6-[3-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 373.4 [M + H]⁺, RT 1.51 min. 705-ethyl-6-[3-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 327.4 [M + H]⁺, RT 1.59 min. 715-ethyl-4-hydroxy-6-[3-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.4 [M + H]⁺ ,RT 1.76 min. 725-ethyl-6-[3-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 341.6 [M + H]⁺, RT 1.72 min. 735-ethyl-4-hydroxy-6-[3-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 357.6 [M + H]⁺, RT 1.87 min. 745-ethyl-6-(4-fluorophenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 278.3 [M + H]⁺, RT 1.06 min. 755-ethyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500MHz, CHCl₃-d) δ ppm 1.17 (t, J = 7.6 Hz, 3H) 2.56 (q, J = 7.6 Hz, 2H)7.48 (dd, J = 7.9, 1.6 Hz, 2H) 7.51-7.63 (m, 3H) 8.56 (s, 1H) 12.77 (br.s., 1H) 13.47 (s, 1H). LC-MS 242.0 [M − H]⁻, 244.3 [M + H]⁺, RT 1.01min. 766-(4-chlorophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.01 (t, J = 7.4 Hz, 3H) 2.36 (q, J =7.6 Hz, 2H) 7.54 (d, J = 8.8 Hz, 1H) 7.62 (d, J = 8.8 Hz, 2H) 8.38 (s,1H) 13.31 (br. s., 1H) 14.93 (br. s., 1H). LC-MS 276.2/278.2 [M − H]⁻,278.1/280.0 [M + H]⁺, RT 1.10 min. 776-(4-chlorophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.98 (t, J = 7.4 Hz, 3H) 2.26 (q, J= 7.4 Hz, 2H) 7.53 (d, J = 8.5 Hz, 2H) 7.62 (d, J = 8.5 Hz, 2H) 12.82(br. s., 1H) 13.92 (s, 1H) 16.18 (br. s., 1H). LC-MS 291.7/293.6 [M −H]⁻, 293.8/295.6 [M + H]⁺, RT 1.35 min. 786-(4-bromophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹HNMR (500 MHz, CHCl₃-d) δ ppm 1.17 (t, J = 7.6 Hz, 3H) 2.53 (q, J = 7.6Hz, 2H) 7.36 (d, J = 8.5 Hz, 2H) 7.73 (d, J = 8.5 Hz, 2H) 8.57 (s, 1H)12.65 (br. s., 1H) 13.43 (s, 1H). LC-MS 319.9/321.9 [M − H]⁻,322.0/324.0 [M + H]⁺, RT 1.41 min. 796-(4-bromophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.98 (t, J = 7.4 Hz, 3H) 2.26 (q, J= 7.4 Hz, 2H) 7.45 (d, J = 8.5 Hz, 2H) 7.76 (d, J = 8.5 Hz, 2H) 12.84(br. s., 1H) 13.92 (s, 1H) 16.22 (br. s., 1H). LC-MS 336.0/338.0 [M −H]⁻, 338.0/340.0 [M + H]⁺, RT 1.60 min. 805-ethyl-6-(4-iodophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹HNMR (500 MHz, DMSO-d₆) δ ppm 1.01 (t, J = 7.4 Hz, 3H) 2.35 (q, J = 7.4Hz, 2H) 7.30 (d, J = 7.9 Hz, 2H) 7.92 (d, J = 7.9 Hz, 2H) 8.38 (s, 1H)13.32 (br. s., 1H) 14.95 (br. s., 1H). LC-MS 367.9 [M − H]⁻, 370.0 [M +H]⁺, RT 1.18 min. 815-ethyl-4-hydroxy-6-(4-iodophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.97 (t, J = 7.3 Hz, 3H) 2.25 (q, J= 7.3 Hz, 2H) 7.29 (d, J = 8.8 Hz, 2H) 7.92 (d, J = 8.8 Hz, 2H) 12.81(br. s., 1H) 13.91 (br. s., 1H). LC-MS 384.0 [M − H]⁻, 386.0 [M + H]⁺,RT 1.36 min. 3126-(5-(dimethylamino)pyrazin-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (3 H, t, J = 7.25Hz), 2.5 (3 H, obscured by DMSO-d₆), 3.15 (6 H, s), 8.24 (1 H, d, J =1.26 Hz), 8.34 (1 H, br. s). LC-MS 305.2 [M + H]⁺, RT 0.72 min. 3135-ethyl-4-hydroxy-2-oxo-6-(5-(pyrrolidin-1-yl)pyrazin-2-yl)-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.07 (3 H, t, J = 7.41Hz), 1.90-2.05 (4 H, m), 2.48 (2 H, m, J = 7.60 Hz), 3.48-3.58 (4 H, m),8.10 (1 H, d, J = 1.26 Hz), 8.33 (1 H, d, J = 1.58 Hz), 12.65 (1 H, br.s), 13.91 (1 H, br. s), 16.16-16.31 (1 H, m). LC-MS 331.2 [M + H]⁺, RT0.78 min. 3146-(5-(3-(dimethylamino)pyrrolidin-1-yl)pyrazin-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.17(t, J = 7.4 Hz, 3 H), 2.01-2.12 (m, 1 H), 2.38-2.47 (m, 1 H), 2.61 (q, J= 7.5 Hz, 2 H), 2.65 (s, 6 H), 3.20-3.29 (m, 1 H), 3.44-3.50 (m, 1 H),3.53-3.62 (m, 1 H), 3.82-3.90 (m, 1 H), 3.93-4.01 (m, 1 H), 8.10 (s, 1H), 8.35 (s, 1 H). LC-MS 374.3 [M + H]⁺, RT 0.78 min. 3445-ethyl-6-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMF) δ ppm 1.43 (t, J = 7.53 Hz, 3 H) 2.74 (q, J =7.54 Hz, 2 H) 4.15 (s, 3 H) 7.01 (d, J = 1.97 Hz, 1 H) 8.02 (d, J = 1.89Hz, 1 H) 8.84 (s, 1 H). LC-MS 248.2 [M + H]⁺, RT 0.48 min. 3455-ethyl-4-hydroxy-6-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.97 (t, J = 7.41 Hz, 3H) 2.52-2.54 (m, 1 H) 3.72-3.75 (m, 3 H) 6.59 (d, J = 1.97 Hz, 1 H) 7.61(d, J = 1.89 Hz, 1 H). LC-MS 262.2 [M − H]⁻, RT 0.63 min. 3465-ethyl-6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.92 (t, J = 7.49 Hz, 3 H) 2.38 (q,J = 7.49 Hz, 2 H) 3.72 (s, 3 H) 7.70 (d, J = 0.79 Hz, 1 H) 8.05 (d, J =0.24 Hz, 1 H) 8.08 (s, 1 H). LC-MS 248.2 [M + H]⁺, RT 0.51 min. 3475-ethyl-4-hydroxy-6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.10-1.13 (m, 3 H)2.51-2.53 (m, 2 H) 3.94 (s, 3 H) 7.85 (d, J = 0.79 Hz, 1 H) 8.21 (s, 1H) 12.46-12.52 (m, 1 H) 13.79-13.85 (m, 1 H). LC-MS 264.2 [M + H]⁺, RT0.62 min.

EXAMPLE 35-ethyl-4-hydroxy-6-(4-((3-iodopropyl)amino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 82)

A mixture of methyl6-(4-(azetidin-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.16 g. 0.47 mmol) and TMSI (0.30 mL, 2.11 mmol) in ACN (1 mL) and DCM(1 mL) was heated in a sealed vial at 60° C. overnight. Additional TMSI(0.30 mL, 2.11 mmol) was added and the heating continued at 60° C. untilcomplete hydrolysis of the ester was observed by LC/MS. The reactionmixture was cooled to room temperature, then diluted with DCM (10 mL)and the reaction was quenched with Na₂S₂O₃ (10% aqueous, 2 mL). Thesolid was filtered and the DCM layer was separated and dried overNa₂SO₄. After removal of the solvent, the residue was purified bypreparative HPLC to afford the title compound (0.0167 g, 8%) as a paleyellow solid.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.3 Hz, 3H) 2.04 (quin, J=6.8Hz, 2H) 2.38 (q, J=7.3 Hz, 2H) 2.51-2.53 (m, 2H, solvent overlap) 3.16(t, J=6.8 Hz, 2H) 6.68 (d, J=8.5 Hz, 2H) 7.21 (d, J=8.5 Hz, 2H) 12.48(s, 1H) 13.84 (br. s., 1H). LC-MS 441.1 [M−H]⁻, 443.1 [M+H]⁺, RT 1.43min.

EXAMPLE 46-(4-(azetidin-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 83)

A mixture of methyl6-(4-(azetidin-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.100 g. 0.30 mmol) and TMSOK (0.33 g mL, 2.21 mmol) in DCM (2 mL) washeated in a sealed vial at 50° C. overnight. The reaction mixture wascooled to room temperature, then diluted with Et₂O (10 mL) and thereaction was quenched with 1M HCl (2 mL). The solid was filtered off andwashed with a DCM/Et₂O mixture. The mother liquor was concentrated andthe residue was triturated with Et₂O. The resulting solid was collectedby filtration and washed with Et₂O, providing the title compound (0.015g, 16%) as a pale yellow solid.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03 (t, J=7.3 Hz, 3H) 2.30-2.39 (m, 4H)3.90 (t, J=7.3 Hz, 4H) 6.51 (d, J=8.5 Hz, 2H) 7.28 (d, J=8.5 Hz, 2H)12.55 (br. s., 1H) 13.86 (br. s., 1H). LC-MS 312.9 [M−H]⁻, 315.2 [M+H]⁺,RT 1.35 min.

EXAMPLE 55-ethyl-6-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 84) Step 1: 1-(3-fluoro-4-morpholinophenyl)butan-1-one

To a solution of 3-fluoro-4-morpholinobenzonitrile (4.38 g, 21.24 mmol)in THF (30 mL) was added nPr-MgCl (2 M Et₂O, 16.0 mL, 32 mmol) at 0° C.The reaction mixture was stirred and allowed to warm to roomtemperature, then heated to reflux for 3 h until the starting materialwas completely consumed. The reaction was quenched by the addition ofNH₄Cl (aqueous saturated, ˜50 mL). A solution of HCl (3M aqueous, 20 mL)was added and the mixture was stirred at room temperature for 30 min.The product was extracted with EtOAc (3×70 mL) then the combinedorganics were washed with NaCl (aqueous saturated) and dried over MgSO₄.The solvents were concentrated and the residue was purified by columnchromatography using EtOAc/hexanes (gradient 0-40%) to afford1-(3-fluoro-4-morpholinophenyl)butan-1-one (2.58 g, 48%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.00 (t, J=7.4 Hz, 3H) 1.76 (sxt, J=7.4Hz, 2H) 2.87 (t, J=7.4 Hz, 2H) 3.19-3.25 (m, 4H) 3.86-3.91 (m, 4H) 6.92(t, J=8.5 Hz, 1H) 7.64 (dd, J=14.0, 2.0 Hz, 1H) 7.70 (dd, J=8.5, 2.0 Hz,1H). LC-MS 252.4 [M+H]⁺, RT 1.32 min.

Step 2:5-ethyl-6-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Using 1-(3-fluoro-4-morpholinophenyl)butan-1-one as prepared above, thetitle compound was prepared according to the procedure of Example 1.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.6 Hz, 3H) 2.41 (d, J=7.6Hz, 2H) 3.09-3.15 (m, 4H) 3.72-3.82 (m, 4H) 7.16 (t, J=8.8 Hz, 1H) 7.27(dd, J=8.8, 1.9 Hz, 1H) 7.38 (dd, J=13.6, 1.9 Hz, 1H) 8.36 (s, 1H) 13.18(br. s., 1H) 14.96 (br. s., 1H). LC-MS 345.0 [M−H]⁻, 347.3 [M+H]⁺, RT1.12 min.

EXAMPLE 65-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 85) Step 1:(S)-1-(4-(3-fluoropyrrolidin-1-yl)phenyl)butan-1-one

A mixture of 4-fluorobenzonitrile (1.80 g, 14.86 mmol),(S)-3-fluoropyrrolidine hydrochloride (2.06 g, 16.41 mmol) and K₂CO₃(5.13 g, 37.11 mmol) in ACN (10 mL) was microwaved at 120° C. for 5 huntil the starting materials were completely consumed. The reactionmixture was diluted with EtOAc/DCM and the resulting solids werefiltered. The mother liquor was concentrated and the residue waspurified by column chromatography using EtOAc/hexanes (gradient 0-40%)to afford (S)-4-(3-fluoropyrrolidin-1-yl)benzonitrile (1.94 g, 69%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 2.09-2.27 (m, 1H) 2.38-2.50 (m, 1H)3.50-3.66 (m, 4H) 5.41 (br. d, J=54.9 Hz, 1H) 6.54 (d, J=8.8 Hz, 2H)7.49 (d, J=8.8 Hz, 2H). LC-MS 191.0 [M+H]⁺, RT 1.13 min.

Step 2: (S)-1-(4-(3-fluoropyrrolidin-1-yl)phenyl)butan-1-one

To a solution of (S)-4-(3-fluoropyrrolidin-1-yl)benzonitrile (2.37 g,12.45 mmol) in THF (12 mL) was added n-PrMgCl (2 M Et₂O, 10.0 mL, 20mmol) at 0° C. The reaction mixture was stirred and allowed to warm toroom temperature and then heated to reflux overnight. The reaction wasquenched by the addition of NH₄Cl (aqueous saturated, ˜50 mL) and theproduct was extracted with EtOAc (3×70 mL). The combined organics werewashed with NaCl (aqueous saturated) and dried over Na₂SO₄. The solventwas concentrated to provide an orange oil that was mixed with 6M HCl (20mL) and stirred at room temperature for 18 h. The mixture wasneutralized with NaHCO₃ solution (aqueous saturated) and the product wasextracted with DCM (3×70 mL). The combined organics were washed withNaCl (aqueous saturated) and dried over Na₂SO₄. The solvents wereconcentrated and the resulting residue was purified by columnchromatography using EtOAc/hexanes (gradient 0-50%) to afford(S)-1-(4-(3-fluoropyrrolidin-1-yl)phenyl)butan-1-one (2.36 g, 81%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.00 (t, J=7.4 Hz, 3H) 1.76 (sxt, J=7.4Hz, 2H) 2.06-2.27 (m, 1H) 2.35-2.48 (m, 1H) 2.86 (t, J=7.4 Hz, 2H)3.49-3.71 (m, 4H) 5.38 (br. d, J=52.0 Hz, 1H) 6.54 (d, J=8.8 Hz, 2H)7.90 (d, J=8.8 Hz, 2H). LC-MS 236.0 [M+H]⁺, RT 1.24 min.

Step 3:5-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Using (S)-1-(4-(3-fluoropyrrolidin-1-yl)phenyl)butan-1-one preparedabove, the title compound was prepared according to the procedure ofExample 1, Steps 3-5 or Example 2, Steps 1 and 2. LC-MS 345.9 [M−H]⁻,347.9 [M+H]⁺, RT 1.31 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 866-[6-(dimethylamino)pyridin-3-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.6 Hz, 3H) 2.63 (q, J= 7.6 Hz, 2H) 3.21 (s, 6 H) 6.66 (d, J = 8.5 Hz, 1H) 7.61 (dd, J = 8.5,2.7 Hz, 2H) 8.32 (d, J = 2.7 Hz, 1H) 8.53 (s, 1H) 12.85 (br. s., 1H)13.57 (s, 1H). LC-MS 285.8 [M − H]⁻, 287.9 [M + H]⁺ RT 0.81 min. 876-[6-(dimethylamino)pyridin-3-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.3 Hz, 3H)2.36 (q, J = 7.3 Hz, 2H) 3.13 (s, 6 H) 6.84 (d, J = 8.2 Hz, 1H) 7.67 (d,J = 8.2 Hz, 1H) 8.19 (d, J = 1.9 Hz, 1H) 12.69 (br. s., 1H) 13.87 (br.s., 1H) 16.23 (br. s., 1H). LC-MS 302.0 [M − H]⁻, 304.0 [M + H]⁺ RT 0.85min. 886-[4-(dimethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.6 Hz, 3H) 2.64 (q, J= 7.6 Hz, 2H) 3.08 (s, 6 H) 6.80 (d, J = 8.8 Hz, 2H) 7.39 (d, J = 8.8Hz, 2H) 8.50 (s, 1H) 12.56 (br. s., 1H) 13.79 (s, 1H). LC-MS 285.0 [M −H]⁻, 287.2 [M + H]⁺, RT 1.09 min. 896-[3-fluoro-4-(morpholin-4-yl)phenyl]-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.12 (s, 3H) 3.02-3.18(m, 4H) 3.71-3.81 (m, 4H) 7.15 (t, J = 8.8 Hz, 1H) 7.31 (d, J = 8.8 Hz,1H) 7.41 (d, J = 13.9 Hz, 1H) 8.32 (s, 1H) 13.18 (br. S., 1H) 15.03 (br.S., 1H). LC-MS 330.9 [M − H]⁻, 332.9 [M + H]⁺, RT 0.92 min. 906-[4-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.4 Hz, 3H)2.38 (q, J = 7.6 Hz, 2H) 2.99 (s, 6 H) 6.81 (d, J = 9.1 Hz, 2H) 7.30 (d,J = 9.1 Hz, 2H) 12.54 (br. s., 1H) 13.87 (br. s., 1H). LC-MS 301.1 [M −H]⁻, 303.2 [M + H]⁺, RT 1.52 min. 916-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]-3-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20(t, J = 7.6 Hz, 3H) 1.51 (s, 9 H) 2.60 (q, J = 7.6 Hz, 2H) 3.14-3.23 (m,4H) 3.61-3.68 (m, 4H) 7.07 (t, J = 8.5 Hz, 1H) 7.18 (dd, J = 12.8, 2.0Hz, 1H) 7.23 (dd, J = 8.5, 2.0 Hz, 1H) 8.55 (s, 1H) 12.62 (br. s., 1H)13.47 (s, 1H). LC-MS 444.0 [M − H]⁻, 446.2 [M + H]⁺, RT 1.46 min. 925-ethyl-6-[3-fluoro-4-(piperazin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03 (t, J =7.4 Hz, 3H) 2.41 (q, J = 7.4 Hz, 2H) 3.19-3.33 (m, 8 H) 7.23 (t, J = 8.8Hz, 1H) 7.29 (dd, J = 8.8, 1.9 Hz, 1H) 7.42 (dd, J = 13.2, 1.9 Hz, 1H)8.37 (s, 1H) 8.83 (br. s., 2H) 13.21 (br. s., 1H) 14.94 (br. s., 1H).LC-MS 343.9 [M − H]⁻, 346.2 [M + H]⁺, RT 0.78 min. 936-[4-(dimethylamino)-3-fluorophenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.6 Hz, 3H) 2.61 (q, J= 7.6 Hz, 2H) 3.03 (d, J = 1.6 Hz, 6 H) 6.95 (t, J = 8.8 Hz, 1H) 7.14(dd, J = 14.0, 2.0 Hz, 1H) 7.19 (dd, J = 8.8, 2.0 Hz, 1H) 8.53 (s, 1H)12.64 (br. s., 1H) 13.57 (s, 1H). LC-MS 303.3 [M − H]⁻, 305.4 [M + H]⁺,RT 1.15 min. 946-[4-(dimethylamino)-3-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.02 (t, J = 7.4 Hz, 3H)2.34 (q, J = 7.4 Hz, 2H) 2.89 (d, J = 0.9 Hz, 6 H) 7.04 (t, J = 8.8 Hz,1H) 7.19 (dd, J = 8.8, 2.0 Hz, 1H) 7.28 (dd, J = 14.3, 2.0 Hz, 1H) 12.66(br. s., 1H) 13.89 (br. s., 1H). LC-MS 319.1 [M − H]⁻, 321.3 [M + H]⁺,RT 1.35 min. 956-[4-(dimethylamino)phenyl]-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (d, J = 6.9 Hz, 6 H) 3.16(spt, J = 6.9 Hz, 1H) 6.83 (d, J = 8.8 Hz, 2H) 7.35 (d, J = 8.8 Hz, 2H)8.58 (s, 1H) 12.21 (br. s., 1H) 13.79 (s, 1H). LC-MS 299.2 [M − H]⁻,301.2 [M + H]⁺, RT 1.08 min. 966-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.32 (d, J = 6.9 Hz, 6H) 3.08-3.14 (m, 1H) 6.82 (d, J = 8.8 Hz, 2H) 7.28 (d, J = 8.8 Hz, 2H)10.68 (br. s., 1H) 13.95 (s, 1H) 14.70 (br. s., 1H). LC-MS 315.2 [M −H]⁻, 317.2 [M + H]⁺ RT 1.35 min. 976-[4-(diethylamino)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.6 Hz, 3H) 1.25 (t, J= 7.3 Hz, 6 H) 2.65 (q, J = 7.6 Hz, 2H) 3.45 (q, J = 7.3 Hz, 4H) 6.78(br. s., 2H) 7.37 (d, J = 8.8 Hz, 2H) 8.50 (s, 1H) 12.25 (br. s., 1H)13.84 (s, 1H). LC-MS 313.1 [M − H]⁻, 315.2 [M + H]⁺ RT 0.91 min. 986-[4-(diethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.5 Hz, 3H) 1.25 (t, J= 7.1 Hz, 6 H) 2.59 (q, J = 7.5 Hz, 2H) 3.44 (q, J = 7.1 Hz, 4H) 6.74(d, J = 8.2 Hz, 2H) 7.32 (d, J = 8.2 Hz, 2H) 11.05 (br. s., 1H) 13.71(s, 1H) 14.71 (s, 1H). LC-MS 329.0 [M − H]⁻, 331.1 [M + H]⁺, RT 1.34min. 995-ethyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.4 Hz, 3H) 2.05-2.10(m, 4H) 2.64 (q, J = 7.5 Hz, 2H) 3.31-3.44 (m, 4H) 6.67 (d, J = 8.8 Hz,2H) 7.38 (d, J = 8.8 Hz, 2H) 8.50 (s, 1H) 12.31 (br. s., 1H) 13.84 (s,1H). LC-MS 310.9 [M − H]⁻, 312.9 [M + H]⁺ RT 1.31 min. 1005-ethyl-4-hydroxy-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J = 7.3 Hz, 3H)2.01-2.13 (m, 4H) 2.58 (q, J = 7.3 Hz, 2H) 3.33-3.44 (m, 4H) 6.65 (d, J= 8.8 Hz, 2H) 7.32 (d, J = 8.8 Hz, 2H) 10.52 (br. s., 1H) 13.72 (s, 1H)14.76 (s, 1H). LC-MS 327.3 [M − H]⁻, 329.2 [M + H]⁺, RT 1.41 min. 1015-ethyl-2-oxo-6-[4-(1H-pyrrol-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H) 2.43 (q, J =7.6 Hz, 2H) 6.32 (t, J = 2.2 Hz, 2H) 7.51 (t, J = 2.2 Hz, 2H) 7.59 (d, J= 8.8 Hz, 2H) 7.77 (d, J = 8.8 Hz, 2H) 8.39 (s, 1H) 13.30 (br. s., 1H)14.98 (br. s., 1H). LC-MS 306.8 [M − H]⁻, 309.0 [M + H]⁺, RT 1.22 min.1026-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.6 Hz,3H) 1.51 (s, 9 H) 2.62 (d, J = 7.6 Hz, 2H) 3.25-3.37 (m, 4H) 3.59-3.67(m, 4H) 7.03 (d, J = 9.1 Hz, 2H) 7.41 (d, J = 9.1 Hz, 2H) 8.53 (s, 1H)12.60 (br. s., 1H) 13.68 (s, 1H). LC-MS 426.3 [M − H]⁻, 428.3 [M + H]⁺,RT 1.26 min. 1035-ethyl-2-oxo-6-[4-(piperazin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J =7.4 Hz, 3H) 2.44 (q, J = 7.4 Hz, 2H) 3.26 (br. s., 4H) 3.44-3.54 (m, 4H)7.12 (d, J = 8.8 Hz, 2H) 7.40 (d, J = 8.8 Hz, 2H) 8.34 (s, 1H) 8.92 (br.s., 2H) 13.12 (br. s., 1H) 14.97 (br. s., 1H). LC-MS 325.9 [M − H]⁻,328.0 [M + H]⁺, RT 0.59 min. 1046-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS 442.0 [M − H]⁻, 444.0 [M + H]⁺RT 1.40 min. 1055-ethyl-4-hydroxy-2-oxo-6-[4-(piperazin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate (1:1) ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.08 (t, J =7.4 Hz, 3H) 2.45 (q, J = 7.4 Hz, 2H) 3.38-3.42 (m, 4H) 3.53-3.57 (m, 4H)7.18 (d, J = 8.8 Hz, 2H) 7.41 (d, J = 8.8 Hz, 2H). LC-MS 342.1 [M − H]⁻,344.4 [M + H]⁺ RT 0.80 min. 1065-ethyl-6-[4-(1H-imidazol-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.4 Hz, 3H) 2.41 (d, J= 7.4 Hz, 2H) 7.28 (s, 1H) 7.68 (d, J = 8.8 Hz, 2H) 7.89 (d, J = 8.8 Hz,2H) 7.97 (s, 1H) 8.40 (s, 1H) 8.64 (s, 1H) 13.45 (br. s., 1H) 14.95 (br.s., 1H). LC-MS 307.8 [M − H]⁻, 309.9 [M + H]⁺, RT 0.59 min. 1075-ethyl-4-hydroxy-6-[4-(1H-imidazol-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.00 (t, J = 7.3 Hz, 3H)2.30 (d, J = 7.3 Hz, 2H) 7.73-7.80 (m, 3H) 7.97 (d, J = 8.5 Hz, 2H) 8.27(s, 1H) 9.44 (br. s., 1H) 12.97 (br. s., 1H) 13.95 (br. s., 1H). LC-MS323.8 [M − H]⁻, 326.0 [M + H]⁺ RT 0.88 min. 1085-ethyl-2-oxo-6-[4-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid Using the 1-minute method: ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t,J = 7.6 Hz, 3H) 1.53-1.79 (m, 6 H) 2.62 (q, J = 7.6 Hz, 2H) 3.27-3.40(m, 4H) 7.01 (d, J = 8.8 Hz, 2H) 7.37 (d, J = 8.8 Hz, 2H) 8.51 (s, 1H)12.35 (br. s., 1H) 13.76 (s, 1H). LC-MS 325.1 [M − H]⁻, 327.1 [M + H]⁺,RT 0.76 min. 1095-ethyl-4-hydroxy-2-oxo-6-[4-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.16 (t, J = 7.4 Hz, 3H) 1.47-1.91(m, 6 H) 2.55 (q, J = 7.4 Hz, 2H) 3.35 (br. s., 4H) 7.06 (br. s., 2H)7.34 (d, J = 7.6 Hz, 2H) 10.80 (br. s., 1H) 13.75 (s, 1H) 14.61 (br. s.,1H). LC-MS 340.9 [M − H]⁻, 343.0 [M + H]⁺ RT 1.56 min. 1105-ethyl-6-[4-(morpholin-4-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.6 Hz, 3H) 2.61 (q, J= 7.6 Hz, 2H) 3.32 (t, J = 5.0 Hz, 4H) 3.90 (t, J = 5.0 Hz, 4H) 7.02 (d,J = 8.8 Hz, 2H) 7.41 (d, J = 8.8 Hz, 2H) 8.53 (s, 1H) 12.37 (br. s., 1H)13.71 (s, 1H). LC-MS 326.8 [M − H]⁻ 329.1 [M + H]⁺, RT 1.82 min. 1116-[4-(azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.19 (t, J = 7.4 Hz, 3H) 2.45(quin, J = 7.3 Hz, 2H) 2.61 (q, J = 7.5 Hz, 2H) 4.02 (t, J = 7.3 Hz, 4H)6.51 (d, J = 8.5 Hz, 2H) 7.33 (d, J = 8.5 Hz, 2H) 8.50 (s, 1H) 12.44(br. s., 1H) 13.77 (s, 1H). LC-MS 296.6 [M − H]⁻ 298.9 [M + H]⁺, RT 1.45min. 1125-ethyl-4-hydroxy-6-(5-morpholinopyridin-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 346.2 [M + H]⁺ RT 0.92 min. 1135-ethyl-4-hydroxy-2-oxo-6-[5-(piperazin-1-yl)pyridin-2-yl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 345.3 [M + H]⁺ RT 0.73 min.

EXAMPLE 7 1-(4-butyrylphenyl)pyrrolidin-2-one

1-(4-Iodophenyl)butan-1-one (1.51 g, 5.50 mmol), pyrrolidin-2-one (0.50mL, 6.52 mmol), CuI (52 mg, 5 mol %),trans-N,N′-dimethylcyclohexane-1,2-diamine (80 mg, 10 mol %) and K₃PO₄(2.34 g, 1.10 mmol) were mixed in toluene (6 mL). The reaction mixturewas heated at 100° C. for 1 h until complete consumption of the startingmaterial was observed. The mixture was diluted with EtOAc/DCM and thesolids were filtered off. The mother liquor was concentrated, theresidue was triturated with Et₂O and the product (1.09 g, 85%) wascollected by filtration.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.01 (t, J=7.4 Hz, 3H) 1.77 (sxt, J=7.4Hz, 2H) 2.20 (quin, J=7.6 Hz, 2H) 2.65 (t, J=8.1 Hz, 2H) 2.93 (t, J=7.4Hz, 2H) 3.91 (t, J=7.1 Hz, 2H) 7.75 (d, J=8.8 Hz, 2H) 7.98 (d, J=8.8 Hz,2H). LC-MS 232.1 [M+H]⁺, RT 1.10 min.

Using the ketone prepared according to the procedure described above,additional compounds described herein may be prepared by substitutingthe appropriate starting materials, reagents and reaction conditions andinclude compounds selected from:

Cpd Name 1145-ethyl-2-oxo-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J = 7.6 Hz, 3H) 2.25(quin, J = 7.6 Hz, 2H) 2.59 (q, J = 7.6 Hz, 2H) 2.69 (t, J = 7.6 Hz, 2H)3.98 (t, J = 7.6 Hz, 2H) 7.51 (d, J = 8.8 Hz, 2H) 7.87 (d, J = 8.8 Hz,2H) 8.55 (s, 1H) 12.94 (br. s., 1H) 13.57 (s, 1H). LC-MS 326.9 [M − H]⁻,324.7 [M + H]⁺, RT 0.94 min. 1155-ethyl-4-hydroxy-2-oxo-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.13 (t, J = 7.4 Hz, 3H)2.24 (quin, J = 7.6 Hz, 2H) 2.51 (q, J = 7.4 Hz, 2H) 2.69 (t, J = 7.6Hz, 2H) 3.96 (t, J = 7.6 Hz, 2H) 7.46 (d, J = 8.8 Hz, 2H) 7.84 (d, J =8.8 Hz, 2H) 11.33 (br. s., 1H) 13.77 (s, 1H) 14.51 (s, 1H). LC-MS 340.6[M − H]⁻, 342.9 [M + H]⁺, RT 1.09 min. 1165-ethyl-6-[4-(2-methyl-5-oxopyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 341.3 [M + H]⁺, RT 0.83 min. 1175-ethyl-6-{4-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.3 [M + H]⁺, RT 0.65 min. 1185-ethyl-2-oxo-6-[4-(3-oxo-2-azaspiro[4.5]dec-2-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 395.3 [M + H]⁺, RT 1.07 min. 1195-ethyl-2-oxo-6-[4-(3-oxo-2-azabicyclo[2.2.1]hept-5-en-2-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 349.0 [M − H]⁻, RT 3.22 min.

EXAMPLE 81-(4-(3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl)phenyl)butan-1-one

A mixture of 1-(4-fluorophenyl)butan-1-one (2.80 g, 16.85 mmol),azetidin-3-ol hydrochloride (2.00 g, 18.26 mmol) and K₂CO₃ (5.10 g,36.90 mmol) in DMSO (20 mL) was heated at 110° C. for 24 h and monitoredby LC/MS. After the starting material was completely consumed, thereaction mixture was cooled to room temperature and diluted with H₂O(˜200 mL). The resulting precipitate was collected by filtration andwashed with H₂O. After drying, the product1-(4-(3-hydroxyazetidin-1-yl)phenyl)butan-1-one (3.32 g, 15.09 mmol) wasdissolved in DCM (40 mL), then TsOH (140 mg, 5 mol %) was added,followed by the addition of 3,4-dihydro-2H-pyran (1.80 mL, 19.66 mmol)dropwise. The reaction mixture was stirred at room temperature for 3 h,then diluted with DCM (150 mL) and washed with NaHCO₃ (aqueoussaturated). The organic layer was dried over Na₂SO₄ and the solventswere concentrated. The resulting residue was purified by columnchromatography using EtOAc/hexanes (gradient 0-60%) to afford1-(4-(3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl)phenyl)butan-1-one(3.70 g, 72%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 0.99 (t, J=7.4 Hz, 3H) 1.48-1.68 (m, 4H)1.70-1.80 (m, 3H) 1.81-1.89 (m, 1H) 2.85 (t, J=7.4 Hz, 2H) 3.48-3.61 (m,1H) 3.82-3.96 (m, 3H) 4.16-4.28 (m, 2H) 4.64-4.75 (m, 2H) 6.40 (d, J=8.5Hz, 2H) 7.86 (d, J=8.5 Hz, 2H).

Using the ketone prepared according to the procedure described above,additional compounds described herein may be prepared by substitutingthe appropriate starting materials, reagents and reaction conditions andinclude compounds selected from:

Cpd Name 1205-ethyl-2-oxo-6-{4-[3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz,CHCl₃-d) δ ppm 1.19 (t, J = 7.6 Hz, 3H) 1.51-1.70 (m, 4H) 1.73-1.81 (m,1H) 1.84-1.90 (m, 1H) 2.60 (q, J = 7.6 Hz, 2H) 3.52-3.60 (m, 1H)3.87-3.94 (m, 2H) 3.96 (dd, J = 8.2, 4.7 Hz, 1H) 4.25 (dt, J = 11.7, 7.1Hz, 1H) 4.70 (dd, J = 4.7, 3.3 Hz, 1H) 4.74 (tt, J = 6.5, 4.7 Hz, 1H)6.55 (d, J = 8.8 Hz, 2H) 7.34 (d, J = 8.8 Hz, 2H) 8.50 (s, 1H) 12.28(br. s., 1H) 13.77 (s, 1H). LC-MS 397.4 [M − H]⁻, 399.9 [M + H]⁺, RT1.27 min.

EXAMPLE 95-ethyl-6-[4-(3-hydroxyazetidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 121)

To a solution of5-ethyl-2-oxo-6-(4-(3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl)phenyl)-1,2-dihydropyridine-3-carboxylicacid (110 mg, 0.28 mmol) in MeOH (1.50 mL) was added concentrated HCl(0.50 mL). The reaction mixture was stirred at room temperature for 20min and then diluted with H₂O (10 mL). The resulting precipitate wascollected by filtration, then washed with H₂O and dried to afford5-ethyl-6-(4-(3-hydroxyazetidin-1-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (45.7 mg, 53%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.6 Hz, 3H) 2.45 (q, J=7.6Hz, 2H) 3.61 (dd, J=8.5, 4.9 Hz, 2H) 4.15 (dd, J=8.5, 6.6 Hz, 2H)4.56-4.67 (m, 1H) 6.52 (d, J=8.5 Hz, 2H) 7.30 (d, J=8.5 Hz, 2H) 8.31 (s,1H) 13.02 (br. s., 1H) 15.00 (br. s., 1H). LC-MS 312.6 [M−H]⁻, 315.1[M+H]⁺, RT 0.90 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 1225-ethyl-6-{4-[(3R)-3-hydroxypiperidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.4 Hz, 3H)1.30-1.40 (m, 1H) 1.45- 1.57 (m, 1H) 1.71-1.81 (m, 1H) 1.87-1.95 (m, 1H)2.46 (q, J = 7.4 Hz, 2H) 2.70 (dd, J = 12.3, 9.1 Hz, 1H) 2.81-2.88 (m,1H) 3.53-3.66 (m, 2H) 3.71 (dd, J = 12.3, 4.7 Hz, 1H) 4.85 (d, J = 4.7Hz, 1H) 7.01 (d, J = 8.8 Hz, 2H) 7.32 (d, J = 8.8 Hz, 2H) 8.30 (s, 1H)13.02 (br. s., 1H) 15.06 (br. s., 1H). LC-MS 341.3 [M − H]⁻, 343.6 [M +H]⁺, RT 0.94 min. 1235-ethyl-6-[4-(3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H) 1.88-1.97(m, 1H) 2.00- 2.11 (m, 1H) 2.48 (q, J = 7.6 Hz, 2H) 3.15 (br. d, J =10.4 Hz, 1H) 3.32-3.44 (m, 2H) 3.46 (dd, J = 10.4, 4.7 Hz, 1H) 4.43 (br.s., 1H) 4.99 (br. s., 1H) 6.62 (d, J = 8.8 Hz, 2H) 7.31 (d, J = 8.8 Hz,2H) 8.30 (s, 1H) 13.01 (br. s., 1H) 15.01 (s, 1H). LC-MS 327.0 [M − H]⁻,329.0 [M + H]⁺, RT 0.91 min.

EXAMPLE 105-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 124)

To a suspension of methyl5-ethyl-4-hydroxy-2-oxo-6-(4-((3R)-3-(tetrahydro-2H-pyran-2-yloxy)pyrrolidin-1-yl)phenyl)-1,2-dihydropyridine-3-carboxylate(0.200 g, 0.45 mmol) in EtOAc (2.5 mL) was added LiI (0.15 g, 1.12mmol). The reaction mixture was heated at 65° C. for 1.5 h untilcomplete ester hydrolysis was observed. The reaction was diluted withEt₂O (15 mL) and a solution of HCl (1M, 4.0 mL) was added. The mixturewas stirred vigorously for 2 h until complete cleavage of theTHP-protecting group was observed by LC/MS. The solid was then collectedby filtration, then washed with H₂O and Et₂O and dried to provide thetitle compound (0.110 g, 69%) as a yellow solid.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.3 Hz, 3H) 1.88-1.98 (m, 1H)2.01-2.10 (m, 1H) 2.39 (q, J=7.3 Hz, 2H) 3.15 (d, J=10.4 Hz, 1H)3.31-3.42 (m, 2H) 3.46 (dd, J=10.4, 4.7 Hz, 1H) 4.34-4.48 (m, 1H) 6.62(d, J=8.5 Hz, 2H) 7.28 (d, J=8.5 Hz, 2H) 12.54 (s, 1H) 13.84 (br. s.,1H). LC-MS 343.0 [M−H]⁻, 345.5 [M+H]⁺, RT 1.14 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 1255-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypiperidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03(t, J = 7.4 Hz, 3H) 1.33-1.44 (m, 1H) 1.53- 1.65 (m, 1H) 1.76-1.86 (m,1H) 1.86-1.95 (m, 1H) 2.34 (q, J = 7.4 Hz, 2H) 2.80 (t, J = 10.7 Hz, 1H)2.94 (t, J = 10.7 Hz, 1H) 3.54-3.73 (m, 3H) 7.17 (br. s., 2H) 7.36 (d, J= 8.8 Hz, 2H) 12.60 (br. s., 1H) 13.87 (br. s., 1H). LC-MS 357.2 [M −H]⁻, 359.5 [M + H]⁺, RT 1.13 min. 1265-ethyl-4-hydroxy-6-[4-(3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.17 (t, J = 7.4 Hz,3H) 2.12-2.26 (m, 2H) 2.55 (q, J = 7.4 Hz, 2H) 3.37 (d, J = 10.7 Hz, 1H)3.46 (td, J = 8.9, 3.0 Hz, 1H) 3.54-3.63 (m, 2H) 4.68 (br. s., 1H) 6.64(d, J = 8.5 Hz, 2H) 7.31 (d, J = 8.5 Hz, 2H) 10.38 (br. s., 1H) 13.71(s, 1H) 14.79 (br. s., 1H). LC-MS 343.1 [M − H]⁻, 345.2 [M + H]⁺, RT1.11 min.

EXAMPLE 11 Step 1: 1-(4-(3-(benzyloxy)pyrrolidin-1-yl)phenyl)butan-1-one

To a suspension of NaH (60% oil, 1.59 g, 39.75 mmol) in THF (30 mL) wasadded a solution of ethyl 4-(3-hydroxypyrrolidin-1-yl)benzoate (6.20 g,26.35 mmol) in THF (30 mL) at 0° C. The reaction was allowed to stir for10 min at this temperature, then a solution of BnBr (4.60 mL, 38.72mmol) in THF (30 mL) was added. The mixture was allowed to warm to roomtemperature and then heated to 50° C. for 3 h. After cooling themixture, the reaction was quenched with NH₄Cl (aqueous saturated) andthe product was extracted with EtOAc (4×90 mL). The organic phase waswashed with NaCl (aqueous saturated), dried over Na₂SO₄ and the solventswere concentrated. The residue was purified by column chromatographyusing EtOAc/hexanes (gradient 20-50%) to afford ethyl4-(3-(benzyloxy)pyrrolidin-1-yl)benzoate (6.25 g, 73%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.38 (t, J=7.1 Hz, 3H) 2.10-2.19 (m, 1H)2.21-2.29 (m, 1H) 3.40-3.49 (m, 2H) 3.50-3.57 (m, 2H) 4.33 (q, J=7.1 Hz,2H) 4.32-4.33 (m, 1H) 4.58 (d, J=12.0 Hz, 1H) 4.60 (d, J=12.0 Hz, 1H)6.52 (d, J=9.1 Hz, 2H) 7.28-7.38 (m, 5H) 7.92 (d, J=8.1 Hz, 2H). LC-MS326.1 [M+H]⁺, RT 1.61 min.

Step 2

To a solution of the ethyl 4-(3-(benzyloxy)pyrrolidin-1-yl)benzoateobtained above (6.25 g, 19.20 mmol) in THF (100 mL) and EtOH (30 mL), asolution of LiOH (1M aqueous, 60.0 mL, 60.00 mmol) and NaOH (1M aqueous,20.0 mL, 20.00 mmol) was added. The mixture was heated at 65° C.overnight, then the solvents were concentrated and the residue wastreated with 3M HCl to pH˜2. The resulting solid was then collected byfiltration and washed with H₂O. After drying, the product4-(3-(benzyloxy)pyrrolidin-1-yl)benzoic acid (5.15 g, 90%) was obtained.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.02-2.23 (m, 2H) 3.34-3.43 (m, 3H) 3.50(dd, J=11.0, 4.7 Hz, 1H) 4.27-4.35 (m, 1H) 4.53 (d, J=12.0 Hz, 1H) 4.56(d, J=12.0 Hz, 1H) 6.55 (d, J=8.8 Hz, 2H) 7.13-7.41 (m, 5H) 7.75 (d,J=8.8 Hz, 2H) 12.05 (br. s., 1H). LC-MS 298.0 [M+H]⁺, RT 1.36 min.

Step 3

To a suspension of 4-(3-(benzyloxy)pyrrolidin-1-yl)benzoic acid (5.15 g,17.32 mmol) in DCM (50 mL) at 0° C., oxalyl chloride (1.90 mL, 21.78mmol) was added dropwise followed by 1 drop of DMF. The reaction mixturewas stirred at 0° C. for 15 min, then was slowly allowed to warm to roomtemperature and stirred for an additional 45 min. The solvent and excessoxalyl chloride were removed by vacuum, then the resulting orange solidwas redissolved in fresh DCM (50 mL) and N,O-dimethylhydroxylaminehydrochloride (2.11 g, 21.63 mmol) was added. The mixture was cooled to0° C. and NEt₃ (6.20 mL, 44.48 mmol) was added dropwise. The reactionmixture was allowed to warm to room temperature, stirred for 30 min,then diluted with DCM (200 mL) and washed with H₂O (2×50 mL). Theorganic phase was dried over Na₂SO₄, then filtered and concentrated toafford a yellowish oil (5.54 g) which was used directly in the nextstep.

Step 4

The product obtained above (5.54 g, 16.27 mmol) was dissolved in THF andthe mixture was cooled to −45° C. A solution of n-PrMgCl (2M Et₂O, 10.5mL, 10.5 mmol) was added dropwise. The reaction mixture was stirred at−45° C. and slowly allowed to warm to room temperature, then stirred foran additional 30 min After complete consumption of the startingmaterial, the reaction was quenched with an NH₄Cl solution (aqueoussaturated) at 0° C. and the product was extracted with EtOAc (3×100 mL).The organic phase was washed with NaCl (aqueous saturated), dried overNa₂SO₄ and the solvents were concentrated. The residue was purified bycolumn chromatography using EtOAc/hexanes (gradient 0-25%) to afford1-(4-(3-(benzyloxy)pyrrolidin-1-yl)phenyl)butan-1-one (3.80 g, 68%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.00 (t, J=7.4 Hz, 3H) 1.76 (sxt, J=7.4Hz, 2H) 2.10-2.19 (m, 1H) 2.22-2.30 (m, 1H) 2.86 (t, J=7.4 Hz, 2H)3.35-3.66 (m, 4H) 4.33 (tt, J=5.1, 2.8 Hz, 1H) 4.58 (d, J=12.0 Hz, 1H)4.60 (d, J=12.0 Hz, 1H) 6.53 (d, J=8.8 Hz, 2H) 7.27-7.40 (m, 5H) 7.89(d, J=8.8 Hz, 2H). LC-MS 324.1 [M+H]⁺, RT 1.46 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 127 methyl6-{4-[3-(benzyloxy)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.16 (t, J = 7.6 Hz, 3H)2.10-2.22 (m, 1H) 2.24- 2.31 (m, 1H) 2.54 (q, J = 7.6 Hz, 2H) 3.29-3.64(m, 4H) 3.93 (s, 3H) 4.31-4.38 (m, 1H) 4.57 (s, 1H) 4.61 (d, J = 12.0Hz, 1H) 6.62 (d, J = 8.8 Hz, 2H) 7.28-7.40 (m, 7 H) 8.23 (s, 1H). LC-MS433.3 [M + H]⁺, RT 1.51 min. 1286-{4-[3-(benzyloxy)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.5 Hz, 3H)2.07-2.25 (m, 1H) 2.24- 2.33 (m, 1H) 2.64 (q, J = 7.5 Hz, 2H) 3.43-3.53(m, 2H) 3.53-3.63 (m, 2H) 4.31-4.39 (m, 1H) 4.61 (s, 2H) 6.66 (d, J =8.5 Hz, 2H) 7.28-7.34 (m, 1H) 7.34-7.41 (m, 6 H) 8.50 (s, 1H) 12.32 (br.s., 1H) 13.84 (s, 1H). LC-MS 417.2 [M − H]⁻, 419.2 [M + H]⁺, RT 1.35min.

EXAMPLE 126-(4-(3-azidopyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 129) Step 1

A solution of methyl6-(4-(3-(benzyloxy)pyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.225 g, 0.52 mmol) in MeOH/AcOH (2:1 mixture) was hydrogenated overPd/C (10%, 100 mg) in a Paar shaker at 60 psi of H₂ for 4 days andmonitored by LC/MS. After complete consumption of starting material, thecatalyst was filtered off and the mixture was washed with DCM. Themother liquor was then concentrated and the residue was treated withH₂O. The resulting solid was collected by filtration, then dried in anN₂-flow and washed with Et₂O to provide methyl5-ethyl-6-(4-(3-hydroxypyrrolidin-1-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate(0.124 g, 69%). LC-MS 343.0 [M+H]⁺, RT 0.94 min.

Step 2

To a solution of the methyl5-ethyl-6-(4-(3-hydroxypyrrolidin-1-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate(44 mg, 0.13 mmol) obtained above was added NEt₃ (60 μL, 0.43 mmol),followed by a mesyl anhydride solution (2M DCM, 0.20 mL, 0.40 mmol) at0° C. The reaction mixture was stirred for 5 min until completeconsumption of the starting material was observed by LC/MS. A mixture ofmono- and di-mesylated products was observed. The reaction mixture wasdiluted with DCM, then washed with H₂O, dried over Na₂SO₄ and thesolvents were removed. The residue was dissolved in DMSO (1 mL) and NaN₃(60 mg, 0.92 mmol) was added. The mixture was heated overnight at 50° C.and then diluted with H₂O. The resulting product was extracted with DCM.The organic phase was dried over Na₂SO₄ and the solvents were removed.The obtained material was dissolved in THF (0.80 mL) and treated withLiOH (1 M aqueous, 0.40 mL, 0.40 mmol). The reaction mixture was heatedat 50° C. for 3 h, then cooled to room temperature and acidified with 1MHCl to pH˜2. The product was extracted with DCM and the organic phasewas dried over Na₂SO₄. The solvents were removed and the crude product(40 mg) was purified by prep HPLC to afford6-(4-(3-azidopyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (6.0 mg, 13%) over 3 steps.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J=7.4 Hz, 3H) 2.21-2.28 (m, 1H)2.29-2.37 (m, 1H) 2.63 (q, J=7.4 Hz, 2H) 3.43 (dd, J=10.4, 2.2 Hz, 1H)3.47-3.60 (m, 2H) 3.65 (dd, J=10.4, 5.5 Hz, 1H) 4.28-4.48 (m, 1H) 6.67(d, J=8.8 Hz, 2H) 7.38 (d, J=8.8 Hz, 2H) 8.51 (s, 1H) 11.99 (br. s., 1H)13.81 (br. s., 1H). LC-MS 352.1 [M−H]⁻, 354.1 [M+H]⁺, RT 1.21 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 130 6-{4-[(3S)-3-azidopyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δppm 1.21 (t, J = 7.4 Hz, 3H) 2.21-2.28 (m, 1H) 2.29-2.37 (m, 1H) 2.63(q, J = 7.4 Hz, 2H) 3.43 (dd, J = 10.4, 2.2 Hz, 1H) 3.47-3.60 (m, 2H)3.65 (dd, J = 10.4, 5.5 Hz, 1H) 4.28-4.48 (m, 1H) 6.67 (d, J = 8.8 Hz,2H) 7.38 (d, J = 8.8 Hz, 2H) 8.51 (s, 1H) 11.99 (br. s., 1H) 13.81 (br.s., 1H). LC-MS 352.1 [M − H]⁻, 354.1 [M + H]⁺, RT 1.21 min.

EXAMPLE 136-(4-(3-aminopyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate (Cpd 131)

A solution of6-(4-(3-azidopyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (5.0 mg) in MeOH (1 mL) and TFA (0.5 mL) was hydrogenated over Pd/C(5 mg) under H₂. After 30 min, complete conversion to the product wasobserved. The catalyst was filtered off and the mother liquor wasconcentrated to afford6-(4-(3-aminopyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (6.0 mg) as a trifluoroacetate salt.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.6 Hz, 3H) 2.08-2.18 (m, 1H)2.29-2.38 (m, 1H) 2.47 (q, J=7.6 Hz, 2H) 3.36-3.44 (m, 2H) 3.50-3.58 (m,1H) 3.61 (dd, J=11.0, 6.3 Hz, 1H) 3.97 (br. s., 1H) 6.68 (d, J=8.8 Hz,2H) 7.35 (d, J=8.8 Hz, 2H) 8.32 (s, 1H) 8.34 (br. s., 3H) 13.10 (s, 1H)15.02 (br. s., 1H). LC-MS 326.0 [M−H]⁻, 328.1 [M+H]⁺, RT 0.70 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 1326-{4-[(3S)-3-aminopyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04(t, J = 7.6 Hz, 3H) 2.08-2.18 (m, 1H) 2.29- 2.38 (m, 1H) 2.47 (q, J =7.6 Hz, 2H) 3.36-3.44 (m, 2H) 3.50-3.58 (m, 1H) 3.61 (dd, J = 11.0, 6.3Hz, 1H) 3.97 (br. s., 1H) 6.68 (d, J = 8.8 Hz, 2H) 7.35 (d, J = 8.8 Hz,2H) 8.32 (s, 1H) 8.34 (br. s., 3H) 13.10 (s, 1H) 15.02 (br. s., 1H).LC-MS 326.1 [M − H]⁻, 328.0 [M + H]⁺, RT 0.69 min. 1336-{4-[(3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.04 (t, J = 7.6 Hz, 3H) 2.47 (q, J = 7.6 Hz, 2H) 3.23(dd, J = 10.7, 2.8 Hz, 4H) 3.41 (dd, J = 10.7, 2.2 Hz, 4H) 3.62-3.78 (m,2H) 4.41 (br. s., 1H) 5.83 (d, J = 3.8 Hz, 1H) 6.67 (d, J = 8.8 Hz, 2H)7.35 (d, J = 8.8 Hz, 2H) 8.32 (s, 1H) 8.41 (br. s., 3H) 13.11 (br. s.,1H) 15.02 (br. s., 1H). LC-MS 342.2 [M − H]⁻, 344.2 [M + H]⁺, RT 0.65min. 1346-{4-[(3R,4R)-3-amino-4-methoxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.04 (t, J = 7.4 Hz, 3H) 2.46 (q, J = 7.4 Hz, 2H)3.35-3.39 (m, 1H) 3.38 (s, 3H) 3.44 (dd, J = 11.5, 2.7 Hz, 1H) 3.65 (dd,J = 11.3, 6.1 Hz, 1H) 3.79 (dd, J = 11.3, 5.4 Hz, 1H) 3.91 (br. s., 1H)4.11-4.18 (m, 1H) 6.70 (d, J = 8.8 Hz, 2H) 7.36 (d, J = 8.8 Hz, 2H) 8.32(s, 1H) 8.44 (br. s., 3H) 13.08 (br. s., 1H) 15.00 (br. s., 1H). LC-MS356.2 [M − H]⁻, 358.5 [M + H]⁺, RT 0.73 min. 1356-{4-[(3R,4S)-3-amino-4-methoxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) LC-MS 356.2 [M −H]⁻, 358.2 [M + H]⁺, RT 0.73 min. 1366-{4-[(3R,4S)-3-amino-4-hydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.4 Hz, 3H) 2.47 (q, J = 7.4 Hz, 2H)3.29-3.39 (m, 2H) 3.60 (dd, J = 10.7, 5.4 Hz, 1H) 3.65 (dd, J = 10.1,7.3 Hz, 1H) 3.85 (br. s., 1H) 4.45-4.54 (m, 1H) 6.66 (d, J = 8.8 Hz, 2H)7.35 (d, J = 8.8 Hz, 2H) 8.17 (br. s., 3H) 8.32 (s, 1H) 13.07 (br. s.,1H) 15.00 (br. s., 1H). LC-MS 342.3 [M − H]⁻, 344.7 [M + H]⁺, RT 0.64min.

EXAMPLE 146-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 137)

Methyl 6-(4-bromophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.106 mg, 0.31 mmol), Pd-catalyst (7.3 mg, 5 mol %) and t-BuONa (0.072g, 0.75 mmol) were mixed under Argon in a heat-gun dried vial. Anhydroustoluene (1.0 mL) was added to the mixture followed by tert-butyl2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.19 g, 0.95 mmol). Thereaction was heated under Argon at 80° C. for 1 hr until completeconsumption of the starting material was observed. The mixture wascooled to room temperature and the reaction was quenched with HCl (1M, 5mL). The product was extracted with DCM (3×7 mL), followed by drying ofthe organic phase over Na₂SO₄. The solvents were concentrated and theresulting residue (0.166 g) was taken used in the step without furtherpurification.

The residue obtained above (0.166 g) was heated in THF (2 mL) with aLiOH solution (1M aqueous, 1.0 mL, 1.0 mmol) at 50° C. for 4 h. Thereaction mixture was cooled to room temperature and acidified with 1 MHCl to pH˜2. The product was extracted with DCM, then the organic phasewas dried over Na₂SO₄ and the solvent concentrated. The resultingresidue was purified by preparative HPLC to provide(S,S)-6-(4-(5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (0.0444 g, 32%) as a yellow solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J=7.6 Hz, 3H) 1.37-1.51 (m, 9H)1.90-2.09 (m, 2H) 2.64 (q, J=7.6 Hz, 2H) 3.17-3.38 (m, 1H) 3.39-3.56 (m,2H) 3.62 (dd, J=15.9, 8.7 Hz, 1H) 4.47-4.76 (m, 2H) 6.66 (d, J=8.2 Hz,2H) 7.37 (d, J=8.6 Hz, 2H) 8.51 (s, 1H) 12.50 (br. s., 1H) 13.81 (br.s., 1H). LC-MS 437.7 [M−H]⁻, 440.0 [M+H]⁺, RT 1.27 min.

EXAMPLE 156-[4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate (1:1) (Cpd 138)

A solution of(S,S)-6-(4-(5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (42.1 mg, 0.096 mmol) in DCM (2 mL) was stirred with TFA (0.5 mL)at room temperature for 30 min. The solvents were removed and Et₂O wasadded to the residue. A yellow solid was filtered off, then washed withEt₂O and dried to afford(S,S)-6-(4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (40.0 mg, 90%) as a trifluoroacetate salt.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J=7.6 Hz, 3H) 1.96 (d, J=10.7Hz, 1H) 2.16 (d, J=10.7 Hz, 1H) 2.46 (q, J=7.6 Hz, 2H) 3.13-3.21 (m, 1H)3.28 (t, J=9.0 Hz, 1H) 3.35 (d, J=10.4 Hz, 1H) 3.65 (d, J=10.4 Hz, 1H)4.51 (br. s., 1H) 4.74 (br. s, 1H) 6.79 (d, J=8.8 Hz, 2H) 7.37 (d, J=8.8Hz, 2H) 8.33 (s, 1H) 8.61 (br. s., 1H) 9.05 (br. s., 1H) 13.08 (br. s.,1H) 15.01 (br. s., 1H). LC-MS 337.7 [M−H]⁻, 340.0 [M+H]⁺, RT 0.72 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 1395-ethyl-6-[4-(2-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.6 Hz, 3H) 1.25 (d, J= 6.0 Hz, 3H) 1.98- 2.22 (m, 4H) 2.64 (q, J = 7.6 Hz, 2H) 3.23-3.33 (m,1H) 3.48-3.53 (m, 1H) 3.95-4.05 (m, 1H) 6.68 (d, J = 8.8 Hz, 2H) 7.35(d, J = 8.8 Hz, 2H) 8.50 (s, 1H) 11.54 (br. s., 1H) 13.86 (br. s., 1H).LC-MS 325.0 [M − H]⁻, 327.2 [M + H]⁺, RT 1.51 min. 1405-ethyl-6-{4-[3-(morpholin-4-yl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS 396.2 [M − H]⁻, 398.3 [M +H]⁺, RT 1.16 min. 1415-ethyl-2-oxo-6-{4-[(2R)-2-(trifluoromethyl)pyrrolidin-1-yl}phenyl}-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21(t, J = 7.4 Hz, 3H) 2.09-2.22 (m, 2H) 2.23- 2.36 (m, 2H) 2.63 (q, J =7.5 Hz, 2H) 3.34-3.41 (m, 1H) 3.72 (t, J = 8.7 Hz, 1H) 4.35 (quin, J =7.3 Hz, 1H) 6.90 (d, J = 8.8 Hz, 2H) 7.40 (d, J = 8.8 Hz, 2H) 8.53 (s,1H) 12.48 (br. s., 1H) 13.71 (br. s., 1H). LC-MS 379.1 [M − H]⁻, 381.2[M + H]⁺, RT 1.57 min. 1425-ethyl-2-oxo-6-{4-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21(t, J = 7.4 Hz, 3H) 2.09-2.22 (m, 2H) 2.23- 2.36 (m, 2H) 2.63 (q, J =7.5 Hz, 2H) 3.34-3.41 (m, 1H) 3.72 (t, J = 8.7 Hz, 1H) 4.35 (quin, J =7.3 Hz, 1H) 6.90 (d, J = 8.8 Hz, 2H) 7.40 (d, J = 8.8 Hz, 2H) 8.53 (s,1H) 12.48 (br. s., 1H) 13.71 (br. s., 1H). LC-MS 378.6 [M − H]⁻, 380.9[M + H]⁺, RT 1.28 min. 1435-ethyl-2-oxo-6-{4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, CHCl₃-d) δ ppm 1.24 (t, J = 7.6 Hz, 3H) 2.01-2.46 (m, 8H) 2.61-2.77 (m, 2H) 3.19 (dd, J = 12.9, 11.0 Hz, 1H) 3.23-3.33 (m, 3H) 3.39 (d,J = 12.9 Hz, 9H) 3.50-3.61 (m, 1H) 3.92 (br. s., 1H) 4.11 (br. s., 1H)4.33 (t, J = 8.2 Hz, 1H) 6.73 (d, J = 8.8 Hz, 2H) 7.45 (d, J = 8.8 Hz,2H) 8.47 (s, 1H) 11.99 (br. s., 1H) 13.29 (br. s., 1H) 14.13 (br. s.,1H). LC-MS 394.2 [M − H]⁻, 396.3 [M + H]⁺, RT 1.15 min. 1446-[4-(3,3-difluoropyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.6 Hz, 3H)2.51-2.65 (m, 4H) 3.65 (t, J = 7.1 Hz, 2H) 3.77 (t, J = 12.9 Hz, 2H)6.67 (d, J = 8.8 Hz, 2H) 7.40 (d, J = 8.8 Hz, 2H) 8.53 (s, 1H) 12.07(br. s., 1H) 13.73 (br. s., 1H). LC-MS 347.0 [M − H]⁻, 349.2 [M + H]⁺,RT 1.50 min. 1455-ethyl-2-oxo-6-[4-(2-phenylpyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J = 7.6 Hz, 3H) 1.96-2.16(m, 3H) 2.47 (tt, J = 11.3, 7.6 Hz, 1H) 2.58 (q, J = 7.6 Hz, 2H) 3.54(td, J = 9.3, 7.6 Hz, 1H) 3.76-3.82 (m, 1H) 4.86 (dd, J = 8.0, 1.7 Hz,1H) 6.59 (d, J = 8.8 Hz, 2H) 7.22 (d, J = 8.8 Hz, 2H) 7.24- 7.28 (m, 3H)7.34 (t, J = 7.6 Hz, 2H) 8.48 (s, 1H) 11.86 (br. s., 1H) 13.78 (br. s.,1H). LC- MS 386.7 [M − H]⁻, 389.0 [M + H]⁺, RT 1.42 min. 1465-ethyl-6-{4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21(t, J = 7.6 Hz, 3H) 1.99-2.18 (m, 4H) 2.64 (q, J = 7.6 Hz, 2H) 3.19-3.33(m, 2H) 3.43 (s, 3H) 3.52 (t, J = 7.7 Hz, 1H) 3.57 (dd, J = 9.5, 3.8 Hz,1H) 4.00 (dt, J = 7.6, 3.8 Hz, 1H) 6.76 (d, J = 8.8 Hz, 2H) 7.37 (d, J =8.8 Hz, 2H) 8.50 (s, 1H) 12.30 (br. s., 1H) 13.82 (br. s., 1H). LC-MS355.2 [M − H]⁻, 357.2 [M + H]⁺, RT 1.50 min. 1475-ethyl-6-{4-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21(t, J = 7.6 Hz, 3H) 1.99-2.18 (m, 4H) 2.64 (q, J = 7.6 Hz, 2H) 3.19-3.33(m, 2H) 3.43 (s, 3H) 3.52 (t, J = 7.7 Hz, 1H) 3.57 (dd, J = 9.5, 3.8 Hz,1H) 4.00 (dt, J = 7.6, 3.8 Hz, 1H) 6.76 (d, J = 8.8 Hz, 2H) 7.37 (d, J =8.8 Hz, 2H) 8.50 (s, 1H) 12.30 (br. s., 1H) 13.82 (br. s., 1H). LC-MS355.1 [M − H]⁻, 357.2 [M + H]⁺, RT 1.14 min. 1486-{4-[(2S,5S)-2,5-bis(methoxymethyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS 399.2 [M − H]⁻, 401.3 [M + H]⁺,RT 1.48 min. 1496-{4-[3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H)1.76-1.93 (m, 1H) 2.16- 2.24 (m, 1H) 2.27 (s, 6 H) 2.48 (q, J = 7.6 Hz,2H) 2.85-2.97 (m, 1H) 3.13 (t, J = 8.7 Hz, 1H) 3.22-3.35 (m, 1H) 3.46(t, J = 8.4 Hz, 1H) 3.53 (t, J = 8.4 Hz, 1H) 6.64 (d, J = 8.5 Hz, 2H)7.32 (d, J = 8.5 Hz, 2H) 8.25 (s, 1H) 12.73 (br. s., 1H) 15.26 (br. s.,1H). LC-MS 354.1 [M − H]⁻, 356.2 [M + H]⁺, RT 1.12 min. 1506-{4-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H) 1.76-1.93 (m, 1H) 2.16-2.24 (m, 1H) 2.27 (s, 6 H) 2.48 (q, J = 7.6 Hz, 2H) 2.85-2.97 (m, 1H)3.13 (t, J = 8.7 Hz, 1H) 3.22-3.35 (m, 1H) 3.46 (t, J = 8.4 Hz, 1H) 3.53(t, J = 8.4 Hz, 1H) 6.64 (d, J = 8.5 Hz, 2H) 7.32 (d, J = 8.5 Hz, 2H)8.25 (s, 1H) 12.73 (br. s., 1H) 15.26 (br. s., 1H). LC-MS 354.1 [M −H]⁻, 356.2 [M + H]⁺, RT 0.70 min. 1516-{4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H) 1.76-1.93 (m, 1H) 2.16- 2.24 (m,1H) 2.27 (s, 6 H) 2.48 (q, J = 7.6 Hz, 2H) 2.85-2.97 (m, 1H) 3.13 (t, J= 8.7 Hz, 1H) 3.22-3.35 (m, 1H) 3.46 (t, J = 8.4 Hz, 1H) 3.53 (t, J =8.4 Hz, 1H) 6.64 (d, J = 8.5 Hz, 2H) 7.32 (d, J = 8.5 Hz, 2H) 8.25 (s,1H) 12.73 (br. s., 1H) 15.26 (br. s., 1H). LC-MS 354.1 [M − H]⁻, 356.2[M + H]⁺, RT 0.70 min. 1525-ethyl-6-[4-(3-fluoropyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.4 Hz, 3H) 2.13-2.31(m, 1H) 2.45 (ddt, J = 18.4, 14.3, 4.0, 4.0 Hz, 1H) 2.64 (q, J = 7.4 Hz,2H) 3.58 (d, J = 4.1 Hz, 1H) 3.60 (d, J = 4.1 Hz, 1H) 3.62-3.71 (m, 2H)5.45 (br. d, J = 52.6 Hz, 1H) 6.69 (d, J = 8.8 Hz, 2H) 7.40 (d, J = 8.8Hz, 2H) 8.51 (s, 1H) 12.29 (br. s., 1H) 13.81 (br. s., 1H). LC-MS 328.8[M − H]⁻, 331.0 [M + H]⁺, RT 1.28 min. 1535-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.4 Hz, 3H)2.13-2.31 (m, 1H) 2.45 (ddt, J = 18.4, 14.3, 4.0, 4.0 Hz, 1H) 2.64 (q, J= 7.4 Hz, 2H) 3.58 (d, J = 4.1 Hz, 1H) 3.60 (d, J = 4.1 Hz, 1H)3.62-3.71 (m, 2H) 5.45 (br. d, J = 52.6 Hz, 1H) 6.69 (d, J = 8.8 Hz, 2H)7.40 (d, J = 8.8 Hz, 2H) 8.51 (s, 1H) 12.29 (br. s., 1H) 13.81 (br. s.,1H). LC-MS 329.1 [M − H]⁻, 331.2 [M + H]⁺, RT 1.43 min. 1545-ethyl-6-{4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.21 (t, J = 7.4 Hz, 3H)2.13-2.31 (m, 1H) 2.45 (ddt, J = 18.4, 14.3, 4.0, 4.0 Hz, 1H) 2.64 (q, J= 7.4 Hz, 2H) 3.58 (d, J = 4.1 Hz, 1H) 3.60 (d, J = 4.1 Hz, 1H)3.62-3.71 (m, 2H) 5.45 (br. d, J = 52.6 Hz, 1H) 6.69 (d, J = 8.8 Hz, 2H)7.40 (d, J = 8.8 Hz, 2H) 8.51 (s, 1H) 12.29 (br. s., 1H) 13.81 (br. s.,1H). LC-MS 329.1 [M − H]⁻, 331.2 [M + H]⁺, RT 1.14 min. 1555-ethyl-2-oxo-6-[4-(phenylamino)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.07 (t, J = 7.4 Hz, 3H) 2.47 (q, J= 7.4 Hz, 2H) 6.94 (t, J = 7.3 Hz, 1H) 7.13-7.19 (m, 4H) 7.28-7.33 (m,2H) 7.36 (d, J = 8.5 Hz, 2H) 8.34 (s, 1H) 8.63 (s, 1H) 13.11 (br. s.,1H) 15.02 (s, 1H). LC-MS 332.6 [M − H]⁻, 334.9 [M + H]⁺, RT 1.21 min.1565-ethyl-2-oxo-6-{4-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J = 7.4 Hz, 3H)2.05-2.33 (m, 3H) 2.44- 2.55 (m, 1H) 2.58 (q, J = 7.4 Hz, 2H) 3.46 (dd,J = 9.5, 7.2 Hz, 0 H) 3.83 (t, J = 9.5 Hz, 0 H) 5.18 (d, J = 7.2 Hz, 1H)6.72 (d, J = 8.8 Hz, 2H) 7.26 (d, J = 3.5 Hz, 1H) 7.33 (d, J = 8.8 Hz,2H) 7.80 (d, J = 3.5 Hz, 1H) 8.49 (s, 1H) 12.29 (br. s., 1H) 13.74 (s,1H). LC-MS 394.2 [M − H⁻, 396.2 [M + H]⁺, RT 1.16 min. 1576-{4-[(2S)-2-carboxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS 355.9 [M − H]⁻, 357.9 [M + H]⁺, RT 0.99 min. 1585-ethyl-6-{4-[methyl(phenyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.20 (t, J = 7.5 Hz, 3H) 2.61 (q, J= 7.5 Hz, 2H) 3.42 (s, 3H) 6.92 (d, J = 8.8 Hz, 2H) 7.24 (t, J = 7.3 Hz,1H) 7.28-7.33 (m, 4H) 7.45 (t, J = 7.3 Hz, 2H) 8.51 (s, 1H) 11.92 (br.s., 1H) 13.81 (br. s., 1H). LC-MS 346.8 [M − H]⁻, 349.1 [M + H]⁺, RT1.39 min. 1596-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.13 (t, J = 7.01 Hz,3H) 2.48-2.53 (m, 2H) 2.86 (br. s., 6 H) 3.25-3.33 (m, 2H) 3.56 (t, J =6.46 Hz, 2H) 6.81 (d, J = 8.75 Hz, 2H) 7.32 (d, J = 8.67 Hz, 2H) 8.35(s, 1H). 1605-ethyl-6-{4-[ethyl(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.08-1.12 (m, 3H) 1.15-1.20 (m, 2H)2.53- 2.57 (m, 2H) 2.93 (s, 3H) 3.46 (d, J = 7.01 Hz, 2H) 6.77 (d, J =8.91 Hz, 2H) 7.31 (d, J = 8.83 Hz, 2H) 8.13 (s, 1H). 1616-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.07(t, J = 7.40 Hz, 3H) 2.54-2.59 (m, 2H) 3.30- 3.37 (m, 11H) 3.51-3.57 (m,2H) 6.78-6.82 (m, 2H) 7.30-7.36 (m, 2H) 8.21-8.27 (m, 1H). LC-MS 344.3[M + H]⁺, RT 0.47. 1626-[4-(1,3-dihydro-2H-isoindol-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.08 (t, J = 7.49 Hz,3H) 2.52-2.54 (m, 2H) 4.72 (s, 4H) 6.81 (d, J = 8.75 Hz, 2H) 7.36 (s,2H) 7.40-7.46 (m, 4H) 8.33 (s, 1H). 1635-isopropyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.14 (d, J = 7.40 Hz, 6 H)1.59-1.70 (m, 2H) 1.74- 1.85 (m, 2H) 2.80-2.95 (m, 1H) 3.46-3.63 (m, 4H)7.23 (d, J = 8.59 Hz, 2H) 7.64 (d, J = 8.59 Hz, 2H) 8.55 (s, 1H). LC-MS325.3 [M − H]⁻, RT 0.83. 1645-cyclopropyl-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.55 (br. s., 4H) 0.75-0.84 (m, 1H)1.66-1.73 (m, 1H) 1.80-1.87 (m, 1H) 2.16-2.24 (m, 1H) 2.25-2.34 (m, 1H)3.41 (s, 1H) 3.49- 3.67 (m, 3H) 6.70 (d, J = 8.91 Hz, 2H) 7.52 (d, J =8.83 Hz, 2H) 7.98 (s, 1H). LC-MS 325.3 [M + H]⁺, RT 0.80. 1656-(4-{[2-(dimethylamino)ethyl](methyl)amino}phenyl)-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03(d, J = 6.94 Hz, 6 H) 2.78-2.88 (m, 1H) 3.23 (s, 9 H) 3.25-3.34 (m, 4H)6.53-6.59 (m, 2H) 7.16-7.23 (m, 2H) 8.24-8.28 (m, 1H) 14.94-15.00 (m,1H). LC-MS 358.3 [M + H]⁺, RT 0.48. 1666-[4-(3-amino-3-methylpyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆): d15.01 (1H, br), 13.11 (1H, br), 8.33 (1H, s), 8.15 (3H, br s), 7.36 (2H,d, J = 8.8 Hz), 6.68 (2H, d, J = 8.8 Hz), 3.60-3.35 (4H, obscurred),2.47 (2H, q, J = 7.5 Hz), 2.38-2.34 (1H, m), 2.22-2.16 (1H, m), 1.49(3H, s), 1.05 (3H, t, J = 7.5 Hz). 1676-[4-(3-{[(carboxymethyl)(methyl)carbamoyl]amino}azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CDCl₃): d8.45 (1H, s), 7.16 (2H, d, J = 8.6 Hz), 6.45 (2H, d, J = 8.6 Hz), 5.12(1H, m), 4.25-4.15 (4H, m), 3.83 (2H, s), 2.94 (3H, s), 2.50 (2H, q, J =7.5 Hz), 0.93 (3H, t, J = 7.5 Hz). 1685-ethyl-6-{4-[3-(5-methyl-2H-tetrazol-2-yl)azetidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CDCl₃): d 13.75 (1H,s), 12.47 (1H, s), 8.55 (1H, s), 7.41 (2H, d, J = 8.6 Hz), 6.66 (2H, d,J = 8.6 Hz), 5.86 (1H, m), 4.64-4.60 (2H, m), 4.56-4.53 (2H, m), 2.63(2H, q, J = 7.3 Hz), 2.62 (3H, s), 1.22 (3H, t, J = 7.3 Hz). 1696-[4-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz, DMSO-d₆): d 14.99(1H, br), 13.06 (1H, br), 8.98 (2H, br), 8.32 (1H, s), 7.33 (2H, d, J =8.7 Hz), 6.69 (2H, d, J = 8.7 Hz), 3.86-3.39 (4H, m), 2.48 (2H,obscurred), 2.14 (2H, m), 1.39 (1H, m), 1.05 (3H, dt, J = 7.0, 6.8 Hz).1706-[4-(3-aminoazetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CDCl₃): δ 8.02 (1H, s), 6.80 (2H, d, J = 8 Hz),6.74 (2H, d, J = 8 Hz), 2.60-2.40 (7H, m), 0.87 (3H, t, J = 7.5 Hz). 1716-[4-(3-{[(benzyloxy)carbonyl]amino}azetidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CDCl₃): δ 8.46 (1H,s), 7.35-7.20 (7H, m), 6.55 (2H, d, J = 8.6 Hz), 5.06 (2H, s), 4.39-4.36(2H, m), 3.90-3.70 (3H, m), 2.53 (2H, q, J = 7.5 Hz), 1.10 (3H, t, J =7.5 Hz). 1726-{4-[3-(diethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆): d13.07 (1H, br), 9.60 (1H, br), 8.33 (1H, s), 7.37 (2H, d, J = 8.8 Hz),6.75 (2H, d, J = 8.8 Hz), 3.80-3.20 (9H, m), 2.47 (2H, q, J = 7.5 Hz),2.24- 2.18 (2H, m), 1.26 (6H, t, J = 7.2 Hz), 1.06 (3H, t, J = 7.5 Hz).1736-{4-[3-(cyclopropylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.27-0.34 (m, 1H)0.41-0.48 (m, 1H) 1.06 (t, J = 7.53 Hz, 4H) 1.42 (d, J = 17.10 Hz, 1H)1.87-1.99 (m, 1H) 2.18 (d, J = 3.39 Hz, 1H) 3.11-3.20 (m, 1H) 3.51 (d, J= 9.38 Hz, 2H) 6.62 (d, J = 8.83 Hz, 2H) 7.32 (d, J = 8.83 Hz, 2H) 8.15(s, 2H) 8.26 (s, 1H). LC-MS: 368.6 [M + H]⁺, RT 0.76 min. 1746-{4-[3-(benzylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm1.03-1.09 (m, 4H) 2.40 (dd, J = 13.99, 6.90 Hz, 2H) 2.44-2.50 (m, 2H)3.37 (d, J = 9.22 Hz, 1H) 3.58 (d, J = 6.86 Hz, 1H) 3.61-3.67 (m, 1H)3.68-3.74 (m, 1H) 3.90-4.01 (m, 1H) 4.27 (br. s., 2H) 6.70 (d, J = 8.91Hz, 2H) 7.33-7.40 (m, 2H) 7.42-7.51 (m, 3H) 7.62-7.70 (m, 2H) 8.33 (s,1H) 9.70-9.90 (m, 1H) 13.10 (br. s., 1H). LC-MS: 418.8 [M + H]⁺, RT 0.83min. 1756-[4-(1,3′-bipyrrolidin-1′-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.19 (t, J = 7.49 Hz, 3H) 2.16 (br.s., 2H) 2.23-2.38 (m, 2H) 2.44-2.66 (m, 3H) 2.70-2.86 (m, 1H) 3.02 (br.s., 2H) 3.41-3.54 (m, 1H) 3.62- 3.72 (m, 1H) 3.74-3.99 (m, 4H) 6.64 (d,J = 8.35 Hz, 2H) 7.34 (d, J = 8.43 Hz, 2H) 8.45 (s, 1H). LC-MS: 382.5[M + H]⁺, RT 0.76 min. 1766-{4-[(1R,5S,6s)-6-(dibenzylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.03 (t, J = 7.41 Hz, 3H) 1.50-1.85 (m, 3H) 2.44 (q,J = 7.57 Hz, 2H) 3.14 (br. s., 2H) 3.35-3.41 (m, 2H) 4.38 (br. s., 2H)4.60 (br. s., 2H) 6.59 (d, J = 8.51 Hz, 2H) 7.29 (d, J = 8.51 Hz, 2H)7.30-7.70 (m, 10 H) 8.31 (s, 1H) 10.55 (br. s., 1H) 13.02 (br. s., 1H)14.99 (br. s., 1H). LC-MS: 518.3 [M − H]⁻, 520.3 [M + H]⁺, RT 1.62 min.1776-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.12(t, J = 7.41 Hz, 3H) 2.07 (br. s., 2H) 2.43 (t, J = 2.21 Hz, 1H) 2.55(q, J = 7.57 Hz, 2H) 3.35-3.40 (m, 2H) 3.72 (d, J = 9.77 Hz, 2H) 6.72(d, J = 8.83 Hz, 2H) 7.33 (d, J = 8.83 Hz, 2H) 8.37 (s, 1H) 8.48 (s,1H). LC-MS: 338.1 [M − H]⁻, 340.5 [M + H]⁺, RT 0.71 min. 1786-{4-[(1R,5S,6s)-6-(benzylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm1.12 (t, J = 7.41 Hz, 3H) 1.85 (br. s., 2H) 2.03 (s, 1H) 2.56 (q, J =7.57 Hz, 2H) 3.30-3.36 (m, 2H) 3.55 (d, J = 9.46 Hz, 2H) 3.89 (s, 2H)4.62 (s, 1H) 6.65 (d, J = 8.83 Hz, 2H) 7.24-7.33 (m, 3H) 7.33-7.41 (m,4H) 7.41-7.48 (m, 1H) 8.36 (s, 1H) 8.52 (s, 1H). LC-MS: 428.2 [M − H]⁻,430.6 [M + H]⁺, RT 0.90 min.

EXAMPLE 165-ethyl-6-[4-(hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride (1:1) (Cpd 179) Step 1:N-(1-(4-bromophenyl)butylidene)-2-methylpropan-2-amine

To a solution of 1-(4-bromophenyl)butan-1-one (6.0 g, 26.4 mmol) andt-butylamine (11 mL, 106 mmol) in DCM (100 mL) was added a 1M solutionof TiCl₄ (16 mL, 16 mmol) dropwise at 0° C. over 30 min. Aftercompletion of the addition, the mixture was stirred at room temperatureovernight, then the reaction was quenched with saturated aqueous NaHCO₃.The product was extracted with DCM and the combined organic phases weredried over Na₂SO₄, then filtered and concentrated to give the titlecompound as a crude product that was used immediately in the next stepwithout further purification.

Step 2:(N-(1-(4-bromophenyl)butylidene)-1-(2,4-dimethoxyphenyl)methanamine

To a solution of 1-(4-bromophenyl)butan-1-one (10.4 g, 45.6 mmol) anddimethoxybenzylamine (7.6 mL, 50.4 mmol) in CH₂Cl₂ (150 mL) was added a1M solution of TiCl₄ (27.4 mL, 27.4 mmol) in CH₂Cl₂ dropwise at 0° C.over 30 min After completion of the addition, the mixture was stirred atroom temperature overnight, then the reaction was quenched withsaturated aqueous sodium bicarbonate. The product was extracted withCH₂Cl₂ and the combined organic phases were dried over Na₂SO₄, thenfiltered and concentrated to give the title compound as a crude productthat was used immediately in the next step without further purification.

Step 3:methyl-6-(4-bromophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate

To a solution of crude(N-(1-(4-bromophenyl)butylidene)-1-(2,4-dimethoxyphenyl)methanamine(15.4 g, 41 mmol) in Ph₂O (20 mL), was added dimethyl2-(methoxymethylene)malonate (7.9 g, 45.4 mmol). The mixture was heatedto 180° C. for 1 hr, and the solution was allowed to cool to roomtemperature. The crude residue was purified on silica gel(EtOAc/hexanes, 0-100% gradient) to afford the title compound as a lightyellow foam (6.0 g, 30%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 0.97 (t, J=7.40 Hz, 3H) 2.06 (q, J=7.51Hz, 2H) 3.50 (s, 3H) 3.78 (s, 3H) 3.97 (s, 3H) 5.04 (s, 2H) 6.24 (d,J=2.44 Hz, 1H) 6.37 (dd, J=8.43, 2.44 Hz, 1H) 6.75-6.81 (m, 2H) 6.83 (d,J=8.43 Hz, 1H) 7.45 (d, J=8.59 Hz, 2H) 8.18 (s, 1H).

Step 4:6-(4-bromophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid

To a suspension ofmethyl-6-(4-bromophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(1.6 g, 3.28 mmol) in THF (5.0 mL) was added LiOH (5.0 mL, 1M solution).The mixture was heated at 50° C. for 3 hrs, then cooled to 0° C. andneutralized with 1M HCl. The precipitate was filtered, then rinsed withEt₂O and dried over an N₂ stream to afford the title compound as a whitesolid (1.3 g, 85%).

Step 5:6-(4-(4-benzylhexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid

6-(4-bromophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (0.4 g, 0.82 mmol),(4aS,7aR)-4-benzyloctahydropyrrolo[3,4-b][1,4]oxazine (0.34 g, 1.0mmol), NaOtBu (0.4 g, 1.2 mmol), and2-(2′-di-tert-butylphosphine)biphenylpalladium(II) acetate (3 mg) wereweighed into a vial. The vial was evacuated and then back filled withArgon. Toluene (3 mL) was added and the vial was sealed and heated to100° C. for 16 hrs. The reaction mixture was cooled to room temperature,then poured into 1M HCl (10 mL) and extracted with DCM. The combinedorganic phase was dried over Na₂SO₄, then filtered and concentrated.

Step 6:5-ethyl-6-[4-(hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride (1:1)

To a solution of crude6-(4-(4-benzylhexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (0.17 g, 0.3 mmol) in CH₂Cl₂ (lmL) was added TFA (1 mL). Thereaction mixture was stirred at room temperature for 1 hr, thenconcentrated and the residue was dissolved in EtOH (5 mL). A solution ofconcentrated HCl (0.5 mL) and 10% Pd/C (0.1 g) was added. The flask wasevacuated and then back filled with H₂. After stirring at roomtemperature for 16 hrs, the reaction mixture was filtered through Celiteand concentrated in vacuo. The crude residue was dissolved in CH₂Cl₂ (2mL) and triturated with Et₂O to afford the title compound as a yellowpowder (41 mg, 43%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.07-1.13 (m, 3H) 2.44-2.49 (m, 2H)3.09-3.18 (m, 1H) 3.25-3.35 (m, 1H) 3.54-3.71 (m, 4H) 3.76-3.83 (m, 1H)3.90-3.99 (m, 1H) 4.02-4.12 (m, 1H) 4.41-4.48 (m, 1H) 6.62-6.68 (m, 2H)7.35-7.41 (m, 2H) 8.31-8.35 (m, 1H). LC-MS 370.3 [M+H]⁺, RT 0.47.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 1806-[4-(4-benzylhexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 0.96 (t, J = 6.98 Hz, 3H) 2.27-2.37 (m, 6 H) 2.47-2.47 (m, 4H) 3.25 (m, , 2H) 3.60 (s, 2H) 6.53-6.62 (m, 2H) 7.20-7.28 (m,2H) 7.28- 7.56 (m, 5H) 8.19 (s, 1H). LC-MS 460.4 [M + H]⁺, RT 0.64. 1816-(4-{3-[(dibenzylamino)methyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.06 (t, J = 7.49 Hz, 3H) 1.54-1.67 (m, 1H) 2.11-2.20 (m, 1H) 2.44-2.50 (m, 2H) 2.74-2.82 (m, 1H) 2.83-2.90 (m, 1H) 3.12(br. s., 1H) 3.17-3.29 (m, 2H) 3.53-3.64 (m, 1H) 4.13-4.20 (m, 1H)4.32-4.42 (m, 2H) 4.43- 4.53 (m, 2H) 6.56 (d, J = 8.75 Hz, 2H) 7.31 (d,J = 8.67 Hz, 2H) 7.40-7.57 (m, 6 H) 7.72 (br. s., 4H) 8.31 (s, 1H)12.96-13.07 (m, 1H). LC-MS 522.3 [M + H]⁺, RT 0.74. 1826-(4-{3-[(benzylamino)methyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.06 (t, J = 7.53 Hz, 3H) 1.81-1.90 (m, 1H) 2.19- 2.29(m, 1H) 2.45-2.49 (m, 2H) 2.77-2.86 (m, 1H) 3.00-3.09 (m, 2H) 3.15-3.22(m, 1H) 3.28-3.36 (m, 1H) 3.37-3.46 (m, 1H) 3.52-3.60 (m, 1H) 4.19 (s,3H) 6.62 (d, J = 8.75 Hz, 2H) 7.34 (d, J = 8.75 Hz, 2H) 7.40-7.50 (m,3H) 7.64 (dd, J = 7.61, 1.54 Hz, 2H) 8.31 (s, 1H) 9.49-9.59 (m, 1H).LC-MS 433.4 [M + H]⁺, RT 0.92. 1836-[4-(3-{[benzyl(methyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.06 (t, J = 7.49 Hz, 3H) 1.74-1.86 (m, 1H) 2.22-2.32 (m, 1H) 2.48 (br. s., 2H) 2.76 (br. s., 3H) 2.83-2.93 (m, 1H)3.03-3.14 (m, 1H) 3.16-3.35 (m, 2H) 3.38-3.54 (m, 2H) 3.60-3.69 (m, 1H)4.28-4.36 (m, 1H) 4.41- 4.51 (m, 1H) 6.64 (br. s., 3H) 7.34 (d, J = 8.59Hz, 3H) 7.49 (br. s., 4H) 7.57-7.65 (m, 3H) 8.32 (s, 1H). LC-MS 446.4[M + H]⁺, RT 0.54. 1845-ethyl-6-(4-{3-[(methylamino)methyl]pyrrolidin-1-yl}phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.06 (t, J = 7.49 Hz, 3H) 1.81-1.90 (m, 1H) 2.16- 2.27(m, 1H) 2.45-2.49 (m, 2H) 2.58 (t, J = 5.40 Hz, 3H) 2.68-2.77 (m, 1H)2.99- 3.07 (m, 2H) 3.15-3.22 (m, 1H) 3.29-3.36 (m, 1H) 3.42-3.48 (m, 1H)3.51-3.58 (m, 1H) 6.63 (d, J = 8.91 Hz, 2H) 7.34 (d, J = 8.83 Hz, 2H)8.32 (s, 1H). LC-MS 356.3 [M + H]⁺, RT 0.47. 1856-(4-{3-[(dimethylamino)methyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.06 (t, J = 7.49 Hz, 3H) 1.82 (dd, J = 11.94, 8.63Hz, 1H) 2.25 (d, J = 6.23 Hz, 1H) 2.44-2.49 (m, 2H) 2.84 (br. s., 6 H)3.13 (t, J = 8.71 Hz, 1H) 3.25 (br. s., 2H) 3.28-3.36 (m, 1H) 3.39 (q, J= 6.96 Hz, 1H) 3.42-3.48 (m, 1H) 3.57-3.63 (m, 1H) 6.65 (d, J = 8.59 Hz,2H) 7.34 (d, J = 8.51 Hz, 2H) 8.32 (s, 1H) 9.94- 10.04 (m, 1H) 13.03(br. s., 1H). LC-MS 370.3 [M + H]⁺, RT 0.49. 1865-ethyl-6-{4-[(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 0.85 (t, J = 7.49 Hz, 3H) 2.22-2.28 (m, 3H) 2.88(br. s., 2H) 3.05-3.12 (m, 2H) 3.33-3.41 (m, 1H) 3.43-3.51 (m, 1H)3.82-3.88 (m, 1H) 4.03 (br. s., 1H) 4.44-4.52 (m, 1H) 6.87 (d, J = 8.83Hz, 2H) 7.21 (d, J = 8.75 Hz, 2H) 8.14 (s, 1H). LC-MS 370.3 [M + H]⁺, RT0.46. 1875-ethyl-6-{4-[(3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.49 Hz, 3H) 1.79-1.89 (m, 1H)1.89- 1.97 (m, 1H) 2.46 (q, J = 7.46 Hz, 2H) 2.90 (br. s., 3H) 3.13-3.22(m, 1H) 3.24-3.31 (m, 1H) 3.41-3.47 (m, 4H) 4.01 (d, J = 11.98 Hz, 1H)4.13-4.20 (m, 1H) 6.80 (d, J = 8.67 Hz, 2H) 7.37 (d, J = 8.83 Hz, 2H)8.33 (s, 1H) 13.06-13.16 (m, 1H). LC-MS 368.3 [M + H]⁺, RT 0.47. 1886-{4-[3-(aminomethyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm0.92 (t, J = 7.40 Hz, 3H) 2.34-2.35 (m, 2H) 2.41- 2.49 (m, 3H) 2.77-2.84(m, 1H) 3.12-3.18 (m, 2H) 3.26-3.32 (m, 1H) 3.32-3.39 (m, 1H) 3.93-4.01(m, 1H) 6.46-6.50 (m, 1H) 7.18-7.23 (m, 2H) 8.11-8.20 (m, 1H). LC-MS342.4 [M + H]⁺, RT 0.47. 1896-{4-[(3aR,6aR)-1-benzylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.49 Hz, 3H) 1.80-1.92 (m, 1H)2.45 (q, J = 7.46 Hz, 3H) 3.20 (dd, J = 11.94, 7.21 Hz, 1H) 3.27 (d, J =9.46 Hz, 2H) 3.47-3.53 (m, 3H) 3.67 (d, J = 11.82 Hz, 1H) 4.34 (d, J =6.78 Hz, 1H) 4.46 (d, J = 4.49 Hz, 2H) 6.65 (d, J = 8.59 Hz, 2H) 7.34(d, J = 8.59 Hz, 2H) 7.47-7.53 (m, 3H) 7.67-7.73 (m, 2H) 8.32 (s, 1H)11.06-11.18 (m, 1H) 13.08 (br. s., 1H). LC-MS 444.7 [M + H]⁺, RT 0.59.1905-ethyl-6-{4-[(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.05 (t, J = 7.53 Hz, 3H) 1.88-1.97 (m, 1H) 2.12-2.24 (m, 1H) 2.46 (d, J = 7.49 Hz, 2H) 3.13-3.30 (m, 3H) 3.37-3.40 (m,1H) 3.40- 3.54 (m, 2H) 3.81-3.90 (m, 1H) 4.30-4.39 (m, 1H) 6.77 (d, J =8.59 Hz, 2H) 7.34-7.41 (m, 2H) 8.33 (s, 1H) 14.97-15.08 (m, 1H). LC-MS354.3 [M + H]⁺, RT 0.46. 1915-ethyl-2-oxo-6-{4-[3-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm1.10-1.15 (m, 3H) 1.88-1.97 (m, 3H) 2.04 (br. s., 4H) 2.55 (q, J = 7.43Hz, 3H) 2.72-2.84 (m, 2H) 2.89-3.03 (m, 2H) 3.19-3.27 (m, 1H) 3.36 (s,2H) 3.40-3.49 (m, 2H) 3.61-3.69 (m, 1H) 6.59 (d, J = 8.35 Hz, 2H) 7.28(d, J = 8.51 Hz, 2H) 8.39 (s, 1H). LC-MS 396.4 [M + H]⁺, RT 0.50. 1926-[4-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.09(t, J = 7.40 Hz, 3H) 3.39 (q, J = 7.01 Hz, 2H) 4.70 (br. s., 2H) 4.75(br. s., 2H) 6.85 (d, J = 8.75 Hz, 2H) 7.36 (dd, J = 7.57, 4.97 Hz, 1H)7.43 (d, J = 8.67 Hz, 2H) 7.87 (d, J = 7.41 Hz, 1H) 8.31 (s, 1H) 8.52(d, J = 4.57 Hz, 1H) 13.09-13.17 (m, 1H) 15.16-15.25 (m, 1H). LC-MS362.2 [M + H]⁺, RT 0.66. 1936-{4-[(3aR,4R,7aS)-4-(dimethylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, CHCl₃-d) δ ppm 8.42-8.51 (m, 1H) 7.35 (d, J = 8.43 Hz, 2H)6.69 (d, J = 7.41 Hz, 2H) 3.74-3.80 (m, 1H) 3.64 (s, 1H) 3.51-3.51 (m,1H) 3.46-3.55 (m, 2H) 3.23 (d, J = 9.14 Hz, 1H) 2.95-2.95 (m, 1H)2.90-2.90 (m, 1H) 2.88-2.88 (m, 1H) 2.91 (dd, J = 16.83, 4.30 Hz, 6 H)2.81-2.82 (m, 1H) 2.54-2.66 (m, 2H) 2.45 (dd, J = 11.78, 5.48 Hz, 1H)2.17 (d, J = 10.33 Hz, 1H) 2.04 (d, J = 13.56 Hz, 1H) 1.93 (d, J = 11.90Hz, 1H) 1.40-1.48 (m, 1H) 1.13-1.36 (m, 6 H). LC-MS 410.6 [M + H]⁺, RT0.85. 1946-(4-{(3aR,4R,7aS)-4-[benzyl(methyl)amino]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1)¹H NMR (500 MHz, CHCl₃-d) δ ppm 8.47 (s, 1H) 7.54 (br. s., 2H) 7.43-7.51(m, 3H) 7.36 (d, J = 8.59 Hz, 2H) 6.67 (d, J = 8.59 Hz, 2H) 3.63-3.81(m, 4H) 3.51-3.61 (m, 2H) 3.48 (t, J = 7.01 Hz, 2H) 3.21 (d, J = 9.22Hz, 2H) 2.76 (br. s., 3H) 2.63 (q, J = 7.51 Hz, 2H) 1.24-1.32 (m, 2H)1.13-1.21 (m, 3H). LC-MS 486.8 [M + H]⁺, RT 1.02. 1955-ethyl-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS396.6 [M + H]⁺, RT 0.85. 1966-{4-[(3aR,4R,7aS)-4-(dibenzylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR(500 MHz, CHCl₃-d) δ ppm 8.48 (s, 2H) 7.59 (br. s., 3H) 7.40-7.50 (m, 7H) 7.36 (d, J = 8.59 Hz, 2H) 6.67 (d, J = 8.59 Hz, 2H) 4.24 (br. s., 4H)3.63-3.81 (m, 3H) 3.46-3.52 (m, 1H) 3.39-3.46 (m, 1H) 3.15 (d, J = 9.46Hz, 1H) 2.63 (d, J = 7.41 Hz, 2H) 2.26-2.37 (m, 1H) 2.16-2.23 (m, 1H)1.93-2.04 (m, 1H) 1.65-1.73 (m, 1H) 1.46- 1.55 (m, 1H) 1.30 (br. s., 2H)1.13-1.23 (m, 3H). LC-MS 562.6 [M + H]⁺, RT 1.27. 1976-{4-[(3aR,4R,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 8.31 (s, 1H) 8.06 (br. s., 1H) 7.35 (d, J = 8.28 Hz,2H) 6.57 (d, J = 8.43 Hz, 2H) 3.21-3.28 (m, 1H) 3.11-3.19 (m, 2H)2.16-2.20 (m, 1H) 1.71-1.77 (m, 2H) 1.49-1.56 (m, 1H) 1.37-1.44 (m, 2H)1.35 (s, 3H) 1.20-1.25 (m, 1H) 1.05 (t, J = 7.25 Hz, 5H). LC-MS 382.5[M + H]⁺, RT 0.83. 1986-{4-[(3aR,4R,6aS)-4-(dimethylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1)LC-MS 396.4 [M + H]⁺, RT 0.79. 1996-{4-[(3aR,4R,6aS)-4-[benzyl(methyl)amino]hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride (1:1) ¹H NMR (500 MHz, CHCl₃-d) δ ppm 8.48 (s, 1H)7.48-7.56 (m, 3H) 7.36 (d, J = 8.28 Hz, 2H) 3.79 (s, 3H) 3.49 (d, J =7.01 Hz, 7 H) 3.37 (d, J = 9.85 Hz, 4H) 2.73-2.81 (m, 2H) 2.61 (d, J =7.57 Hz, 2H) 1.15-1.23 (m, 3H). LC-MS 472.6 [M + H]⁺, RT 0.97. 2005-ethyl-6-{4-[(3aR,4R,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) LC-MS 382.3 [M + H]⁺, RT 0.81. 2016-{4-[(3aR,4R,6aS)-4-(dibenzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.26-8.31 (m, 1H) 7.28-7.39 (m,11H) 7.17- 7.25 (m, 2H) 6.64-6.72 (m, 2H) 3.73-3.82 (m, 2H) 3.64-3.72(m, 1H) 3.43-3.59 (m, 3H) 3.11-3.21 (m, 2H) 2.99-3.11 (m, 2H) 2.74-2.84(m, 1H) 1.81-1.90 (m, 1H) 1.64- 1.72 (m, 1H) 1.32-1.44 (m, 2H) 1.07 (s,3H). LC-MS 548.5 [M + H]⁺, RT 1.40. 2026-{4-[(3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS368.3 [M + H]⁺, RT 0.86. 2036-{4-[(3aR,4S,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 8.23-8.29 (m, 1H) 7.92 (s, 1H) 7.25-7.34 (m, 2H)6.48-6.58 (m, 2H) 3.13-3.33 (m, 1H) 1.81-1.97 (m, 1H) 1.52-1.52 (m, 1H)1.46- 1.71 (m, 5H) 1.13-1.44 (m, 7 H) 1.05 (t, J = 7.45 Hz, 3H). LC-MS382.3 [M + H]⁺, RT 0.92. 2046-{4-[(3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS366.7 [M − H]⁻, RT 0.80. 2056-(4-{(3aR,7aS)-3a-[(dimethylamino)methyl]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1)¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.27 (s, 1H) 7.30 (d, J = 8.67 Hz, 2H)6.60 (d, J = 8.75 Hz, 2H) 3.35 (d, J = 8.35 Hz, 1H) 3.22-3.32 (m, 2H)3.16 (d, J = 9.69 Hz, 1H) 2.74 (d, J = 13.71 Hz, 1H) 2.43-2.57 (m, 2H)2.30 (s, 6 H) 2.19 (d, J = 13.71 Hz, 1H) 2.05- 2.13 (m, 1H) 1.58-1.75(m, 2H) 1.24-1.55 (m, 6 H) 1.06 (t, J = 7.49 Hz, 3H). LC-MS 425.3 [M +H]⁺, RT 0.65. 2066-{4-[(3aR,6aS)-5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.00-1.07 (m, 3H) 2.42-2.48 (m, 4H) 2.98 (q, J= 9.0 Hz, 1H) 3.12 (br. s., 1H) 3.28-3.39 (m, 1H) 3.40-3.50 (m, 2H) 3.57(d, J = 10.1 Hz, 1H) 3.69 (br. s., 1H) 4.32-4.45 (m, 2H) 6.58-6.84 (m,2H) 7.30-7.39 (m, 2H) 7.43-7.52 (m, 3H) 7.54-7.65 (m, 2H) 8.32 (s, 1H)10.89 (br. s., 1H) 13.08 (br. s., 1H). LC-MS 442.3 [M − H]⁻, 444.6 [M +H]⁺, RT 0.87 min. 2075-ethyl-6-{4-[(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,MeOH-d₄) δ ppm 1.12 (t, J = 7.6 Hz, 3H) 2.55 (q, J = 7.6 Hz, 2H)3.26-3.34 (m, 4H) 3.43-3.57 (m, 4H) 3.58-3.69 (m, 2H) 6.87 (d, J = 8.8Hz, 2H) 7.38 (d, J = 8.8 Hz, 2H) 8.45 (s, 1H). LC-MS 352.2 [M − H]⁻,354.2 [M + H]⁺, RT 0.87 min. 2085-ethyl-6-{4-[(3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.6 Hz, 3H) 2.46 (q, J = 7.6 Hz,2H) 2.76-2.93 (m, 4H) 3.14 (br. s., 1H) 3.21-3.28 (m, 1H) 3.29-3.37 (m,2H) 3.40-3.50 (m, 2H) 3.50-3.59 (m, 2H) 3.86 (br. s., 1H) 6.62-6.84 (m,2H) 7.35 (d, J = 8.5 Hz, 2H) 8.32 (s, 1H) 9.91-10.53 (m, 1H) 13.08 (br.s., 1H) 15.02 (br. s., 1H). LC-MS 366.3 [M − H]⁻, 368.0 [M + H]⁺, RT1.16 min. 2096-[4-(3,6-diazabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03 (t, J = 7.6 Hz, 3H)2.40 (q, J = 7.6 Hz, 2H) 3.25 (d, J = 12.0 Hz, 2H) 3.44 (s, 2H) 3.59 (d,J = 12.0 Hz, 2H) 7.21 (d, J = 8.5 Hz, 2H) 7.40 (d, J = 8.5 Hz, 2H) 8.31(s, 1H) 15.20 (br. s., 1H). LC-MS 324.2 [M − H]⁻, 326.5 [M + H]⁺, RT0.61 min. 2105-ethyl-6-{4-[(1S,5R,6R)-6-(methylamino)-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500MHz, MeOH-d₄) δ ppm 1.12 (t, J = 7.6 Hz, 3H) 1.89-2.01 (m, 1H) 2.55 (q,J = 7.6 Hz, 2H) 2.64 (s, 3H) 2.69-2.78 (m, 1H) 3.07 (d, J = 9.1 Hz, 1H)3.23 (dd, J = 11.3, 8.2 Hz, 1H) 3.39-3.48 (m, 1H) 3.66 (d, J = 9.1 Hz,1H) 3.74-3.94 (m, 3H) 6.97 (d, J = 8.2 Hz, 2H) 7.38 (d, J = 8.2 Hz, 2H)8.41 (s, 1H). LC-MS 366.1 [M − H]⁻, 368.5 [M + H]⁺, RT 0.81 min. 2116-{4-[(1S,5R,6R)-6-amino-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.05(t, J = 7.3 Hz, 3H) 1.75-1.95 (m, 1H) 2.47 (q, J = 7.3 Hz, 2H) 2.88-2.97(m, 1H) 3.03 (dd, J = 8.8, 5.7 Hz, 3H) 3.12-3.20 (m, 1H) 3.21-3.30 (m,1H) 3.52 (d, J = 9.8 Hz, 1H) 3.80 (br. s., 1H) 3.93 (d, J = 9.8 Hz, 1H)3.96- 4.09 (m, 1H) 6.81 (d, J = 8.2 Hz, 2H) 7.37 (d, J = 8.2 Hz, 2H)8.33 (br. s., 1H) 13.12 (br. s., 1H). LC-MS 352.3 [M − H]⁻, 354.3 [M +H]⁺, RT 0.80 min. 2126-{4-[(1S,5R,6S)-6-amino-3-azabicyclo[3.2.0]hept-3-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ ppm 1.05 (t, J = 7.6 Hz, 3H) 2.08 (ddd, J = 12.6, 8.8, 3.5Hz, 1H) 2.26-2.37 (m, 1H) 2.47 (q, J = 7.6 Hz, 2H) 3.00-3.16 (m, 4H)3.52-3.55 (m, 1H) 3.62 (d, J = 9.8 Hz, 1H) 3.66 (d, J = 10.4 Hz, 1H)6.84 (d, J = 8.8 Hz, 2H) 7.36 (d, J = 8.8 Hz, 2H) 8.24 (br. s., 3H) 8.33(s, 1H) 13.10 (br. s., 1H). LC-MS 352.3 [M − H]⁻, 354.3 [M + H]⁺, RT0.82 min. 2135-ethyl-6-[4-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) LC-MS: 368.5 [M +H]⁺, RT 1.20 min. 2146-[4-(7-amino-5-azaspiro[2.4]hept-5-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS: 354.6 [M + H]⁺, RT 0.53min. 2155-ethyl-6-{4-[(3aR,5r,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate(1:1) LC-MS: 382.4 [M + H]⁺, RT 0.55 min. 2166-{4-[(3S,4R)-3-(aminomethyl)-4-methylpyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 356.3 [M + H]⁺, RT 0.55 min.2176-(4-{3-[1-(benzylamino)cyclopropyl]pyrrolidin-1-yl}phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 0.90-1.12 (m, 7 H) 1.56-1.67 (m, 1H) 2.12- 2.23 (m,4H) 2.87-2.98 (m, 2H) 3.44 (d, J = 8.12 Hz, 2H) 3.66 (s, 1H) 4.37 (br.s., 2H) 6.66 (d, J = 8.83 Hz, 2H) 7.34 (d, J = 8.67 Hz, 2H) 7.42-7.51(m, 3H) 7.56 (d, J = 6.94 Hz, 2H) 8.31 (s, 1H). 2186-{4-[3-(1-aminocyclobutyl)pyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm1.05 (t, J = 7.49 Hz, 3H) 1.77-1.95 (m, 2H) 1.97- 2.09 (m, 1H) 2.12-2.31(m, 5H) 2.44-2.49 (m, 2H) 2.66-2.76 (m, 1H) 3.19 (t, J = 9.73 Hz, 1H)3.32 (td, J = 9.65, 6.94 Hz, 1H) 3.46-3.56 (m, 2H) 6.66 (d, J = 8.83 Hz,2H) 7.34 (d, J = 8.75 Hz, 2H) 8.31 (s, 1H). 2196-[4-(3a-cyanooctahydro-2H-isoindol-2-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.07 (t, J = 7.57 Hz,3H) 1.44-1.56 (m, 3H) 1.57- 1.67 (m, 4H) 1.67-1.79 (m, 2H) 1.86-1.95 (m,1H) 2.56 (q, J = 7.25 Hz, 2H) 2.73 (t, J = 5.04 Hz, 1H) 3.33 (t, J =8.67 Hz, 1H) 3.47 (t, J = 8.67 Hz, 1H) 3.56-3.66 (m, 2H) 6.58 (d, J =8.83 Hz, 2H) 7.33 (d, J = 8.51 Hz, 2H) 7.88 (s, 1H). LCMS 392.7 [M +H]⁺, RT 1.28 min. 220(3aR,6aR)-2-[4-(5-carboxy-3-ethyl-6-oxo-1,6-dihydropyridin-2-yl)phenyl]hexahydrocyclopenta[c]pyrrole-3a(1H)-carboxylic acidtrifluoroacetate (1:1) ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.57Hz, 3H) 1.65-2.49 (m, 7 H) 2.59- 2.71 (m, 2H) 3.03-3.28 (m, 3H)3.56-3.74 (m, 1H) 4.20 (m, 1H) 6.82-7.17 (m, 2H) 7.36-7.58 (m, 2H)8.56-8.62 (m, 1H) 12.88 (br. s., 1H). LCMS 397.3 [M + H]⁺, RT 1.18 min.2216-{4-[3-(dimethylamino)pyrrolidin-1-yl]-2-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 374.5 [M + H]⁺, RT 0.54 min.2225-ethyl-6-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 343.4 [M + H]⁺, RT 0.65 min. 223 6-{4-[4-(dimethylamino)piperidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 370.5 [M + H]⁺, RT 0.76 min. 2245-ethyl-6-[4-(4-methoxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 357.4 [M + H]⁺, RT 0.89 min. 2255-ethyl-6-{2-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 347.4 [M + H]⁺, RT 0.95 min.2265-ethyl-2-oxo-6-{4-[3-(pyridin-4-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid LC-MS: 390.3 [M + H]⁺, RT 0.70 min. 2275-ethyl-2-oxo-6-{4-[3-(pyridin-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid LC-MS: 390.3 [M + H]⁺, RT 1.09 min. 2286-[4-(4-aminopiperidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid LC-MS: 342.3 [M + H]⁺, RT 0.83 min. 2305-ethyl-2-oxo-6-{4-[3-(1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid LC-MS: 380.3 [M + H⁺, RT 1.02 min. 2316-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]-2-fluorophenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS:358.3 [M + H]⁺, RT 0.79 min. 2325-ethyl-6-[4-(3-ethyl-3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 357.3 [M + H]⁺, RT 0.98 min. 2335-ethyl-6-[4-(3-hydroxy-3-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 343.3 [M + H]⁺, RT 1.04 min. 2346-[4-(3-{[(2-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 468.3 [M + H]⁺, RT 1.33 min.2356-{4-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 356.3 [M + H]⁺, RT 0.93 min.2366-[4-(3-{[(3-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 466.3 [M + H]⁺, RT 0.84 min.2376-[4-(3-{[(4-chlorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 466.4 [M + H]⁺, RT 1.24 min.2385-ethyl-6-[4-(3-{[(3-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 450.4 [M + H]⁺, RT 1.18 min.2395-ethyl-6-[4-(3-{[(4-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 450.4 [M + H]⁺, RT 1.12 min.2405-ethyl-6-[4-(3-{[(2-fluorobenzyl)amino]methyl}pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 450.4 [M + H]⁺, RT 1.17 min.2415-ethyl-2-oxo-6-[4-(3-{[(pyridin-3-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 433.4 [M + H]⁺, RT 0.95 min.2425-ethyl-2-oxo-6-[4-(3-{[(pyridin-4-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 433.4 [M + H]⁺, RT 0.99 min.2435-ethyl-2-oxo-6-[4-(3-{[(pyridin-2-ylmethyl)amino]methyl}pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylic acid LC-MS: 433.4 [M + H]⁺, RT 1.07 min.2446-{4-[(3aR,4S,7aS)-4-azidooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS 408.3[M + H]⁺, RT 1.45. 2456-{4-[(3aR,4S,6aS)-4-azidohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS394.8 [M + H]⁺, RT 1.36.

EXAMPLE 175-ethyl-6-{4-[(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride (1:1) (Cpd 246) Step 1

A solution of 1-(4-chlorophenyl)butan-1-one (5.00 g, 27.37 mmol) andt-butyl amine (11.60 mL, 109.90 mmol) in DCM (30 mL) was cooled to 0° C.A solution of TiCl₄ (1M DCM, 18.00 mL, 18.00 mmol) was added dropwisevia syringe pump over 30 min. The reaction mixture was allowed to warmto room temperature and stirred overnight. The mixture was diluted withDCM (200 mL) and then the reaction was quenched with NaHCO₃ (aqueoussaturated, 60 mL). After vigorous shaking, the organic phase wasseparated using a PTFE phase separator, then dried over Na₂SO₄. Thesolvent was removed to afford a colorless oil (5.30 g, 81), which wasused directly in the next step without further purification.

The oil (2.14 g, 8.99 mmol) and triethylmethane tricarboxylate (2.20 mL,10.46 mmol) in diglyme (9 mL) were heated at 160° C. for 2 h. After themixture was cooled to room temperature, a white solid was collected byfiltration and washed with Et₂O. The resulting product (1.54 g, 53%) wasobtained as a colorless crystalline material.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.95 (t, J=7.4 Hz, 3H) 1.30 (t, J=7.1Hz, 3H) 2.18 (d, J=7.4 Hz, 2H) 4.34 (q, J=7.1 Hz, 2H) 7.44 (d, J=8.2 Hz,2H) 7.57 (d, J=8.2 Hz, 2H) 11.43 (br. s., 1H) 13.57 (s, 1H). LC-MS322.2/324.2 [M+H]⁺, RT 1.30 min.

Step 2

To a solution of ethyl6-(4-chlorophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(1.00 g, 3.11 mmol), PPh₃ (2.00 g, 7.63 mmol) and BnOH (0.80 mL, 7.72mmol) in THF (20 mL) at 0° C. was added DIAD (1.50 mL, 7.57 mmol)dropwise. The reaction mixture was stirred at 0° C. for 15 min andallowed to warm to room temperature, then stirred for 30 min. The THFwas concentrated and the residue was purified by column chromatography(EtOAc/hexanes, 0-20% gradient) to afford ethyl2,4-bis(benzyloxy)-6-(4-chlorophenyl)-5-ethylnicotinate (1.00 g, 64%) asa white solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.03 (t, J=7.4 Hz, 3H) 1.32 (t, J=7.1Hz, 3H) 2.55 (q, J=7.4 Hz, 2H) 4.38 (q, J=7.1 Hz, 2H) 5.15 (s, 2H) 5.42(s, 2H) 7.27-7.48 (m, 14H). LC-MS 502.1 [M+H]⁺, RT 1.83 min.

A mixture of ethyl2,4-bis(benzyloxy)-6-(4-chlorophenyl)-5-ethylnicotinate (0.94 g, 1.87mmol) and TMSOK (90%, 0.60 g, 4.21 mmol) in THF (7.5 mL) was heated at70° C. in a sealed vial overnight. The THF was removed under reducedpressure and H₂O (2 mL) was added to the residue. The mixture wasacidified with 1M HCl to pH˜1 and the product was extracted with DCM(4×10 mL). After drying the organic phase over Na₂SO₄, the solvents wereremoved and the residue was triturated with hexanes. The resulting solidwas filtered and washed with hexanes, affording the product (0.726 g,82%) as a colorless solid

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.03 (t, J=7.4 Hz, 3H) 2.56 (q, J=7.4Hz, 2H) 5.17 (s, 2H) 5.50 (s, 2H) 7.28-7.49 (m, 14H). LC-MS 474.2/476.4[M+H]⁺, RT 1.67 min.

Step 3

2,4-bis(benzyloxy)-6-(4-chlorophenyl)-5-ethylnicotinic acid (0.2 g, 0.4mmol), (3aR,6aR)-1-benzyloctahydropyrrolo[3,4-b]pyrrole (0.16 g, 0.8mmol), NaOtBu (0.12 g, 1.2 mmol) and2-(2′-di-tert-butylphosphine)biphenylpalladium(II) acetate (3 mg, 3 mol%) were weighed into a vial. The vial was evacuated and then back filledwith Argon. Toluene (2 mL) was added and the vial was sealed and heatedto 100° C. for 16 hrs. The reaction mixture was cooled to roomtemperature, then poured into 1M HCl and extracted with DCM. Thecombined organic phase was dried over Na₂SO₄, then filtered andconcentrated. The crude residue was dissolved in MeOH (5 mL) and 10%Pd(OH)₂/C was added. Under H₂, the reaction mixture was stirred at roomtemperature for 2 hrs. The mixture was then filtered through Celite andconcentrated. The crude residue was dissolved in CH₂Cl₂ and 2M HCl/Et₂O(1 mL) was added. The yellow precipitate was filtered and rinsed withEt₂O to afford the title compound (58 mg, 40%).

¹H NMR (500 MHz, DMSO-d₆) δ 1.03 (t, J=7.41 Hz, 3H) 1.88-1.96 (m, 1H)2.13-2.23 (m, 1H) 2.37 (q, J=7.30 Hz, 2H) 3.14-3.28 (m, 3H) 3.34-3.53(m, 3H) 3.82-3.89 (m, 1H) 4.31-4.38 (m, 1H) 6.77 (d, J=8.83 Hz, 2H) 7.34(d, J=8.67 Hz, 2H). LC-MS 370.4 [M+H]⁺, RT 0.51.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 2476-(4-{3-[1-(dimethylamino)cyclopropyl]pyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δppm 0.92-1.11 (m, 7 H) 2.06 (s, 4H) 2.37 (s, 2H) 2.70-2.85 (m, 8 H)2.88-2.99 (m, 1H) 3.10-3.28 (m, 2H) 3.58-3.71 (m, 2H) 6.60- 6.73 (m, 2H)7.23-7.35 (m, 2H) 13.83 (br. s., 1H). 2486-{4-[(3aR,5r,6aS)-5-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 384.3 [M +H]⁺, RT 0.68 min. 2496-(4-{(3S,4R)-3-[(dibenzylamino)methyl]-4-methylpyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 552.5 [M +H]⁺, RT 0.93 min. 2506-{4-[(3aR,5r,6aS)-5-(benzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 474.4[M + H]⁺, RT 0.71 min. 2516-{4-[(3aR,5r,6aS)-5-(dibenzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS:565.0 [M + H]⁺, RT 0.89 min. 2526-[4-(7-amino-5-azaspiro[2.4]hept-5-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS: 368.3[M + H]⁺, RT 0.68 min. 2536-{4-[1-(tert-butoxycarbonyl)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 484.6 [M +H]⁺, RT 1.00 min. 2545-ethyl-4-hydroxy-6-(4-{3-[(methylamino)methyl]pyrrolidin-1-yl}phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆) δ 1.04 (s, 3H) 1.81-1.91 (m, 1H) 2.16-2.27 (m, 1H) 2.34-2.43(m, 2H) 2.58 (s, 3H) 2.69-2.78 (m, 1H) 2.99-3.08 (m, 2H) 3.14-3.21 (m,1H) 3.28-3.37 (m, 1H) 3.40 (s, 2H) 3.50-3.57 (m, 1H) 6.59-6.66 (m, 2H)7.28-7.35 (m, 2H) 9.10 (br. s, 1H) 12.57 (br. s, 1H) 13.86 (br. s, 1H).LC-MS 372.3 [M + H]⁺, RT 0.55. 2556-[4-(3-{[benzyl(methyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ0.91 (t, J = 7.37 Hz, 3H) 1.78-1.88 (m, 1H) 2.18 (s, 3H) 2.53-2.57 (m,4H) 2.67-2.76 (m, 1H) 2.95-3.05 (m, 2H) 3.09-3.15 (m, 1H) 3.22-3.30 (m,1H) 3.38 (s, 1H) 3.43-3.50 (m, 1H) 6.48-6.57 (m, 2H) 6.88-6.93 (m, 2H)6.99-7.05 (m, 2H) 7.18-7.28 (m, 3H) 9.10-9.24 (m, 1H) 13.80-13.87 (m,1H). 2565-ethyl-4-hydroxy-6-{4-[(3aR,4R,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride (1:1) ¹H NMR (500 MHz, MeOH-d₄) δ 1.12 (t, J = 7.37 Hz,3H) 1.71-1.80 (m, 1H) 1.83- 1.94 (m, 1H) 2.06-2.16 (m, 1H) 2.18-2.26 (m,1H) 2.46-2.54 (m, 2H) 2.83 (s, 3H) 3.02-3.10 (m, 1H) 3.20-3.27 (m, 1H)3.35-3.40 (m, 1H) 3.51 (m, J = 7.00 Hz, 2H) 3.55-3.61 (m, 1H) 3.67-3.75(m, 1H) 6.86-6.92 (m, 2H) 7.35-7.41 (m, 2H). LC-MS 398.3 [M + H]⁺, RT0.89. 2576-[4-(1,3′-bipyrrolidin-1′-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz, MeOH-d₄) δ 0.98 (t,J = 7.41 Hz, 1H) 1.92-2.00 (m, 1H) 2.06- 2.16 (m, 1H) 2.19-2.28 (m, 1H)2.36 (q, J = 7.40 Hz, 2H) 2.45-2.54 (m, 1H) 3.11- 3.18 (m, 1H) 3.30-3.37(m, 1H) 3.50-3.61 (m, 2H) 3.61-3.67 (m, 2H) 3.67-3.73 (m, 1H) 3.95-4.03(m, 1H) 6.66-6.73 (m, 2H) 7.21-7.27 (m, 2H). LC-MS 396.1 [M − H]⁻, RT0.52. 2586-{4-[(3aR,4S,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, MeOH-d₄) δ 1.13 (t, J = 7.41 Hz, 3H) 1.51-1.61 (m, 1H) 1.67-1.86 (m, 4H) 2.02-2.10 (m, 1H) 2.34-2.41 (m, 1H) 2.52 (m, 2H) 2.75-2.86(m, 1H) 3.15-3.23 (m, 1H) 3.36-3.45 (m, 2H) 3.47-3.53 (m, 1H) 3.64-3.69(m, 1H) 6.75 (m, J = 8.91 Hz, 2H) 7.35 (m, J = 8.83 Hz, 2H). LC-MS 398.3[M + H]⁺, RT 0.90. 2596-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, MeOH-d₄) δ 1.24-1.35 (m, 1H), 1.47-1.57 (m, 1H), 1.92-2.01 (m,1H), 2.03-2.11 (m, 1H), 2.45-2.55 (m, 1H), 2.83 (s, 3H), 3.52-3.59 (m,1H), 6.70-6.76 (m, 2H), 7.34-7.41 (m, 2H). LC-MS 342.3 [M + H]⁺, RT0.51. 2604-hydroxy-5-methyl-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) ¹H NMR (500 MHz, MeOH-d₄) δ 1.13 (t, J = 7.41 Hz, 3H), 1.51-1.61(m, 1H), 1.67- 1.86 (m, 4H), 2.02-2.10 (m, 1H), 2.34-2.41 (m, 1H), 2.52(m, 2H), 2.75-2.86 (m, 4H), 3.15-3.23 (m, 1H), 3.36-3.45 (m, 2H),3.47-3.53 (m, 1H), 3.64-3.69 (m, 1H), 6.75 (m, J = 8.9 Hz, 2H), 7.35 (m,J = 8.8 Hz, 2H). LC-MS 398.3 [M + H]⁺, RT 0.84. 2616-{4-[(3aR,4R,7aS)-4-(dimethylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1)¹H NMR (500 MHz, CHCl₃-d) δ ppm 7.30 (d, J = 8.35 Hz, 2H) 6.66 (d, J =9.38 Hz, 2H) 4.12 (d, J = 6.62 Hz, 2H) 3.22 (s, 1H) 2.92 (s, 1H) 2.90(br. s., 1H) 2.54 (br. s., 6 H) 2.05 (br. s., 4H) 2.02-2.02 (m, 4H) 1.26(br. s., 4H) 1.17 (br. s., 5H). LC-MS 426.8 [M + H]⁺, RT 0.99. 2626-{4-[(3aR,4R,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 8.02 (br. s., 2H) 7.31 (d, J = 8.83 Hz, 3H)6.57 (d, J = 8.83 Hz, 2H) 3.21-3.28 (m, 1H) 3.16 (s, 1H) 2.28-2.42 (m,5H) 1.70-1.80 (m, 2H) 1.47-1.64 (m, 2H) 1.29-1.37 (m, 1H) 0.96-1.10 (m,6 H). LC-MS 396.7 [M − H]⁻, RT 0.99. 2636-{4-[(3aR,4R,6aS)-4-(dimethylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride (1:1) ¹H NMR (500 MHz, CHCl₃-d) δ ppm 7.30 (d, J = 8.59Hz, 2H) 6.69-6.69 (m, 2H) 6.72 (d, J = 8.67 Hz, 2H) 3.83-3.93 (m, 1H)3.57 (dd, J = 9.73, 6.42 Hz, 1H) 3.41-3.53 (m, 3H) 3.33 (d, J = 9.30 Hz,1H) 3.14 (br. s., 1H) 2.95 (d, J = 18.76 Hz, 6 H) 2.54 (q, J = 7.36 Hz,2H) 2.06-2.21 (m, 2H) 1.71-1.84 (m, 1H) 1.19-1.24 (m, 1H) 1.16 (t, J =7.37 Hz, 3H). LC-MS 412.7 [M + H]⁺, RT 0.93. 2646-{4-[(3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1)¹H NMR (500 MHz, DMSO-d₆) δ ppm 7.33 (d, J = 8.75 Hz, 2H) 6.71 (d, J =8.67 Hz, 2H) 3.42-3.53 (m, 1H) 3.20-3.29 (m, 2H) 2.97-3.06 (m, 2H)2.84-2.92 (m, 1H) 2.61- 2.68 (m, 1H) 2.36 (s, 2H) 1.85-2.00 (m, 2H)1.68-1.76 (m, 1H) 1.53-1.61 (m, 1H) 0.98-1.09 (m, 3H). LC-MS 384.3 [M +H]⁺, RT 0.94. 2656-{4-[(3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.15 (s, 1H) 7.25 (d, J = 8.75 Hz,2H) 6.65 (d, J = 8.75 Hz, 2H) 3.27-3.45 (m, 4H) 3.13-3.20 (m, 1H)2.88-2.97 (m, 1H) 2.71 (br. s., 1H) 2.32-2.41 (m, 2H) 2.03-2.14 (m, 2H)1.62-1.72 (m, 1H) 1.49 (s, 1H) 0.97-1.06 (m, 3H). LC-MS 384.7 [M + H]⁺,RT 0.93. 2666-(4-{(3aR,7aS)-3a-[(dimethylamino)methyl]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 13.84 (br. s., 1H)7.29 (br. s., 3H) 6.65 (br. s., 3H) 3.33 (br. s., 1H) 2.74-2.92 (m, 10H) 1.48 (br. s., 6 H) 1.04 (br. s., 9 H). LC-MS 438.8 [M − H]⁻, RT 1.07.2675-ethyl-4-hydroxy-6-{4-[(3aR,4S,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acidhydrochloride (1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 7.31 (d, J = 8.43Hz, 2H) 6.71 (d, J = 8.20 Hz, 2H) 3.43 (br. s., 2H) 3.32-3.39 (m, 2H)3.15-3.24 (m, 1H) 2.62 (br. s., 3H) 2.37 (d, J = 7.01 Hz, 2H) 2.03-2.19(m, 1H) 1.68-1.77 (m, 1H) 1.46-1.54 (m, 1H) 1.32-1.38 (m, 1H) 1.14-1.18(m, 1H) 0.99-1.08 (m, 3H) 0.78-0.85 (m, 1H). LC-MS 398.8 [M + H]⁺, RT0.96. 2685-ethyl-4-hydroxy-6-{4-[(3aR,4S,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 7.30 (d, J = 8.75 Hz, 2H) 6.61 (d,J = 8.83 Hz, 2H) 3.61-3.68 (m, 1H) 3.28-3.42 (m, 4H) 3.15-3.24 (m, 1H)2.53-2.72 (m, 5H) 2.38 (d, J = 7.57 Hz, 3H) 1.92-2.01 (m, 1H) 1.31-1.68(m, 4H) 1.01-1.08 (m, 3H). LC-MS 412.7 [M + H]⁺, RT 0.99. 2696-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1)(1R,5S,6s)-N,N-dibenzyl-3-azabicyclo[3.1.0]hexan-6-amine was preparedaccording to literature procedure Chem. Eur. J. 2002, 8, 3789-3801. ¹HNMR (500 MHz, MeOH-d₄) δ ppm 1.09 (t, J = 7.41 Hz, 3H) 2.12-2.21 (m, 2H)2.47 (q, J = 7.41 Hz, 2H) 2.53 (t, J = 2.13 Hz, 1H) 3.39 (d, J = 9.38Hz, 2H) 3.76 (d, J = 9.62 Hz, 2H) 6.75 (d, J = 8.75 Hz, 2H) 7.31 (d, J =8.75 Hz, 2H). LC-MS: 354.3 [M − H]⁻, 356.3 [M + H]⁺, RT 0.85 min. 2705-ethyl-4-hydroxy-6-{4-[(1R,5S,6s)-6-(methylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.02 (t, J = 7.29 Hz, 3H) 2.29(br. s., 2H) 2.35 (q, J = 7.29 Hz, 2H) 2.59-2.68 (m, 4H) 3.33 (d, J =9.30 Hz, 2H) 3.64 (d, J = 9.77 Hz, 2H) 6.68 (d, J = 8.51 Hz, 2H) 7.28(d, J = 8.51 Hz, 2H) 9.29 (br. s., 1H) 12.58 (s, 1H) 13.84 (br. s., 1H).LC-MS 368.3 [M − H]⁻, 370.3 [M + H]⁺, RT 0.85 min. 2716-{4-[(1R,5S,6s)-6-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1)¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.02 (t, J = 7.29 Hz, 3H) 2.35 (q, J =7.29 Hz, 2H) 2.37-2.44 (m, 2H) 2.52-2.54 (m, 1H) 2.88 (s, 6 H) 3.29-3.33(m, 2H) 3.66 (d, J = 9.85 Hz, 2H) 6.68 (d, J = 8.75 Hz, 2H) 7.29 (d, J =8.75 Hz, 2H) 12.60 (s, 1H) 13.84 (s, 1H). LC-MS 382.3 [M − H]⁻, 384.3[M + H]⁺, RT 0.84 min. 2725-ethyl-4-hydroxy-6-[4-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,MeOH-d₄) δ ppm 1.09 (t, J = 7.3 Hz, 3H) 1.79-2.03 (m, 4H) 2.48 (q, J =7.3 Hz, 2H) 2.85-2.95 (m, 1H) 3.09 (td, J = 11.7, 3.0 Hz, 1H) 3.31-3.36(m, 1H) 3.42-3.52 (m, 1H) 3.57 (t, J = 9.5 Hz, 1H) 3.61 (d, J = 11.7 Hz,1H) 3.74 (dd, J = 11.7, 4.4 Hz, 1H) 3.99 (t, J = 4.4 Hz, 1H) 6.79 (d, J= 8.8 Hz, 2H) 7.37 (d, J = 8.8 Hz, 2H). LC-MS 382.1 [M − H]⁻, 384.3 [M +H]⁺, RT 0.85 min. 2735-ethyl-4-hydroxy-6-{4-[(3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.01 (t, J = 7.4 Hz, 3H) 2.34 (q,J = 7.4 Hz, 2H) 2.77 (s, 3H) 3.02-3.27 (m, 4H) 3.28-3.42 (m, 2H) 3.47(d, J = 9.1 Hz, 2H) 3.54 (br. s., 2H) 6.75 (d, J = 8.5 Hz, 2H) 7.29 (d,J = 8.5 Hz, 2H). LC-MS 382.3 [M − H]⁻, 383.9 [M + H]⁺, RT 1.25 min. 2745-ethyl-6-{4-[(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.02 (t, J = 7.4 Hz, 3H) 2.36 (q, J = 7.4 Hz,2H) 3.00-3.20 (m, 4H) 3.21-3.34 (m, 1H) 3.35-3.51 (m, 5H) 6.71 (d, J =8.8 Hz, 2H) 7.31 (d, J = 8.8 Hz, 2H) 9.76 (br. s, 2H) 12.59 (s, 1H)13.85 (br. s., 1H). LC-MS 368.2 [M − H]⁻, 370.0 [M + H]⁺, RT 1.08 min.2756-{4-[3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,MeOH-d₄) δ ppm 1.09 (t, J = 7.4 Hz, 3H) 2.26-2.39 (m, 1H) 2.47 (d, J =7.4 Hz, 2H) 2.57-2.69 (m, 1H) 3.00 (s, 6 H) 3.39-3.48 (m, 1H) 3.58-3.64(m, 1H) 3.69 (td, J = 8.7, 3.5 Hz, 1H) 3.81 (t, J = 8.7 Hz, 1H)4.05-4.13 (m, 1H) 6.81 (d, J = 8.5 Hz, 2H) 7.36 (d, J = 8.5 Hz, 2H).LC-MS 370.1 [M − H]⁻, 372.9 [M + H]⁺, RT 0.82 min. 2766-[4-(3a-cyanooctahydro-2H-isoindol-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) ¹H NMR (500MHz, DMSO-d₆) δ ppm 1.03 (t, J = 7.41 Hz, 3H) 1.50 (d, J = 4.41 Hz, 3H)1.62 (br. s., 2H) 1.72 (dd, J = 9.93, 4.26 Hz, 2H) 2.34-2.41 (m, 2H)2.74 (s, 1H) 3.32- 3.37 (m, 2H) 3.49 (dd, J = 9.77, 7.88 Hz, 2H)3.60-3.68 (m, 2H) 6.66 (d, J = 8.83 Hz, 2H) 7.31 (d, J = 8.83 Hz, 2H)12.59 (br. s., 1H) 13.84 (s, 1H). LCMS 408.3 [M + H]⁺, RT 1.49 min. 2776-[4-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆): d 13.86 (1H, br), 12.60 (1H, br), 9.44 (1H, br), 9.05 (2H,br), 8.53 (1H, br), 7.31 (2H, d, J = 8.7 Hz), 6.70 (2H, d, J = 8.7 Hz),2.95-2.90 (1H, m), 2.88-2.83 (1H, m), 2.36 (2H, q, J = 7.4 Hz),2.18-1.39 (5H, m). 2786-[4-(2,8-diazaspiro[4.5]dec-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,DMSO-d₆): d 13.84 (1H, br), 12.57 (1H, br), 9.00 (1H, br), 8.94 (1H,br), 7.29 (2H, d, J = 8.7 Hz), 6.65 (2H, d, J = 8.7 Hz), 4.30 (4H, br),3.20-3.05 (4H, m), 2.38 (2H, q, J = 7.4 Hz), 2.06-1.75 (6H, m), 1.10(3H, t, J = 7.4 Hz). 2796-{4-[3-(2-aminopropan-2-yl)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) ¹H NMR (500 MHz,MeOH-d₄) δ ppm 1.11 (t, J = 7.41 Hz, 3H) 1.39-1.47 (m, 6 H) 1.92- 2.03(m, 1H) 2.14-2.25 (m, 1H) 2.34-2.46 (m, 1H) 2.49 (q, J = 7.25 Hz, 2H)2.62- 2.70 (m, 1H) 3.37-3.44 (m, 1H) 3.47-3.54 (m, 1H) 3.59 (t, J = 8.83Hz, 1H) 6.74 (d, J = 8.83 Hz, 2H) 7.33 (d, J = 8.20 Hz, 2H). LC-MS:384.4 [M − H]⁻, 386.3 [M + H]⁺, RT 0.84 min. 2805-ethyl-4-hydroxy-6-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 359.5 [M + H]⁺, RT 0.87 min. 2816-{4-[4-(benzyloxy)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 449.5 [M + H]⁺, RT 1.45 min.2825-ethyl-4-hydroxy-6-[4-(4-methoxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 373.5 [M + H]⁺, RT 1.14 min. 2836-{4-[4-(dibenzylamino)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 538.7 [M + H]⁺, RT 1.00 min.2846-[4-(4-aminopiperidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 358.5 [M + H]⁺, RT 0.68 min. 2856-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 356.3 [M + H]⁺, RT 0.73min. 2865-ethyl-4-hydroxy-2-oxo-6-{4-[3-(pyridin-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid LC-MS: 406.3 [M + H]⁺, RT 1.30 min.2875-ethyl-4-hydroxy-2-oxo-6-{4-[3-(1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylic acid LC-MS: 396.3 [M + H]⁺, RT 1.50 min.2885-ethyl-6-[4-(3-ethyl-3-hydroxypyrrolidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 373.3 [M + H]⁺, RT 1.47 min.2895-ethyl-4-hydroxy-6-[4-(3-hydroxy-3-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 357.3 [M − H]⁻, RT 1.08 min.2906-{4-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 372.4 [M + H]⁺, RT 0.88 min.2916-{4-[3-(dimethylamino)pyrrolidin-1-yl]-2-fluorophenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 390.4 [M + H]⁺, RT 0.73 min.2925-ethyl-6-{2-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 363.4 [M + H]⁺, RT 0.97 min.2935-ethyl-6-{2-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 365.3 [M + H]⁺, RT 1.50 min.2946-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS 456.8 [M +H]⁺, RT 1.42. 2956-[4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid trifluoroacetate (1:1) LC-MS 356.4[M + H]⁺, RT 0.81. 2965-ethyl-4-hydroxy-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride(1:1) ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.18 (s, 1H) 7.24 (d, J = 8.51 Hz,2H) 6.49 (d, J = 8.67 Hz, 2H) 3.22-3.44 (m, 5H) 3.06-3.14 (m, 1H)2.74-2.87 (m, 1H) 2.63 (s, 3H) 2.27-2.43 (m, 3H) 1.84-1.94 (m, 1H)1.71-1.81 (m, 1H) 1.56-1.65 (m, 1H) 1.43- 1.55 (m, 1H) 1.23-1.36 (m, 1H)1.05-1.23 (m, 1H) 1.00 (t, J = 7.33 Hz, 3H). LC-MS 412.5 [M + H]⁺, RT1.02. 2975-ethyl-6-{4-[(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride (1:1) LC-MS381.7 [M + H]⁺, RT 1.66. 3154-hydroxy-5-methyl-2-oxo-6-(5-(pyrrolidin-1-yl)pyridin-2-yl)-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.04 (s, 3 H) 2.10-2.21(m, 4 H) 3.63-3.78 (m, 4 H) 7.03-7.12 (m, 1 H) 7.51-7.62 (m, 1 H)8.09-8.17 (m, 1 H) 12.59 (br. s, 1 H) 13.97 (br. s, 1 H). LC-MS: 316.2[M + H]⁺, RT 0.69 min. 3166-(5-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-2-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.04(s, 3 H) 2.11-2.19 (m, 2 H) 3.41 (s, 6 H) 3.61-3.83 (m, 5 H) 7.05-7.12(m, 1 H) 7.55-7.60 (m, 1 H) 8.10-8.16 (m, 1 H) 12.41- 12.67 (m, 1 H)13.82-14.09 (m, 1 H). LC-MS: 359.2 [M + H]⁺, RT 0.58 min. 3176-(5-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)pyridin-2-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz,DMSO-d₆) δ ppm 2.05 (s, 3 H) 2.44 (1H, s) 3.29 (2H, d, J = 10 Hz) 3.62(2H, d, J = 10 Hz) 3.63-3.78 (m, 4 H) 7.09-7.17 (m, 1 H) 7.60-7.65 (m, 1H) 8.16-8.21 (m, 1 H) 8.98-9.22 (m, 1 H) 9.93-10.06 (m, 1 H) 12.44-12.61(m, 1 H) 13.83-13.97 (m, 1 H), 2.15 (2H, s). LC-MS: 343.2 [M + H]⁺, RT0.60 min. 3186-(4-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-2-methylphenyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid NMR: (DMSO-d⁶, 500MHz): δ 1.72 (3H, s), 2.09 (3H, s), 2.15 (2H, s), 2.44 (1H, s), 3.29(2H, d, J = 10 Hz), 3.62 (2H, d, J = 10 Hz), 6.52 (1H, dd, J = 8 Hz, 2.5Hz), 6.54 (1H, s), 7.05 (1H, d, J = 8 Hz), 8.41 (3H, m), 12.63 (1H, s),13.83 (1H, s). LC-MS: 356.2 [M + H]⁺, RT 1.17 min. 3195-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.11 (t, J= 5 Hz, 3H), 2.02-2.09 (m, 2H), 2.26-2.30 (m, 2H), 2.48 (q, J = 1 Hz,2H), 2.92 (s, 3H), 3.10-3.15 (m, 2H), 3.52-3.55 (m, 2H), 3.77 (s, 2H),3.86 (s, 2H), 6.63 (d, J = 8 Hz, 2H), 7.33 (d, J = 8 Hz, 2H). LC-MS398.3 [M + H]⁺, RT 0.55 min. 3206-(4-(2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.11 (t, J= 7 Hz, 3H), 2.11-2.13 (m, 4H), 2.48 (q, J = 7 Hz, 2H), 3.25-3.27 (m,4H), 3.82 (s, 4H), 6.63 (d, J = 8 Hz, 2H), 7.33 (d, J = 8 Hz, 2H). LC-MS384.3 [M + H]⁺, RT 0.54 min. 3216-(4-(2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.12 (t, J= 7 Hz, 3H), 2.13-2.21 (m, 4H), 2.51 (q, J = 1 Hz, 2H), 3.42-3.56 (m,8H), 6.75 (d, J = 8 Hz, 2H), 7.34 (d, J = 8 Hz, 2H). LC-MS 384.5 [M +H]⁺, RT 0.55 min. 3225-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.12 (t, J= 7 Hz, 3H), 2.13-2.35 (m, 4H), 2.51 (q, J = 1 Hz, 2H), 3.03 (s, 3H),3.19-3.29 (m, 2H), 3.47-3.55 (m, 4H), 3.73-3.76 (m, 2H), 6.75 (d, J = 8Hz, 2H), 7.34 (d, J = 8 Hz, 2H). LC-MS 398.3 [M + H]⁺, RT 0.55 min. 3236-(4-(2,5-diazaspiro[3.4]octan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.12 (t, J= 7 Hz, 3H), 2.13-2.34 (m, 4H), 2.51 (q, J = 7 Hz, 2H), 3.41-3.50 (m,3H), 3.60-3.65 (m, 1H), 4.09-4.12 (m, 1H), 4.25-4.27 (m, 1H), 6.75 (d, J= 8 Hz, 2H), 7.34 (d, J = 8 Hz, 2H). LC-MS 370.3 [M + H]⁺, RT 0.51 min.3246-(4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOD-d₆) δ 1.10 (t, J= 7 Hz, 3H), 2.46 (q, J = 1 Hz, 2H), 4.17 (s, 4H), 4.34 (s, 4H), 6.63(d, J = 8 Hz, 2H), 7.33 (d, J = 8 Hz, 2H). LC-MS 356.3 [M + H]⁺, RT 0.51min. 3255-ethyl-6-(4-(ethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, MeOD-d₆) δ 1.10 (t, J = 7 Hz, 3H), 1.40 (t, J = 7Hz, 3H), 2.43 (q, J = 7 Hz, 2H), 3.49 (q, J = 7 Hz, 2H), 7.52 (d, J = 8Hz, 2H), 7.65 (d, J = 8 Hz, 2H). LC-MS 303.3 [M + H]⁺, RT 1.21 min. 3265-ethyl-4-hydroxy-6-(4-(methylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, MeOD-d₆) δ 1.10 (t, J = 7 Hz, 3H), 2.44 (q, J = 7Hz, 2H), 3.07 (s, 3H), 7.39 (d, J = 8 Hz, 2H), 7.58 (d, J = 8 Hz, 2H).LC-MS 289.3 [M + H]⁺, RT 1.14 min.

EXAMPLE 186-[4-(dimethylamino)phenyl]-5-ethyl-4-methoxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 298) Step 1

To a solution of 1-(4-(dimethylamino)phenyl)butan-1-one (5.65 g, 29.54mmol) in DCM (35 mL) was added benzylamine (3.50 mL, 32.01 mmol) andNEt₃ (10.0 mL, 71.74 mmol). The mixture was cooled to 0° C., then aTiCl₄ solution (1M DCM, 17.0 mL, 17.0 mmol) was added dropwise viasyringe pump over 30 min. The reaction mixture was allowed to warm toroom temperature and stirred overnight. The mixture was diluted with DCM(100 mL) and then the reaction was quenched with NaHCO₃ (aqueoussaturated, 30 mL). After vigorous shaking, the organic phase wasseparated using a PTFE phase separator, then dried over Na₂SO₄. Removalof the solvent afforded the title product (7.37 g, 89%) as a yellow oil,which was used directly in the next step without further purification.

Step 2

Crude 4-(1-(benzylimino)butyl)-N,N-dimethylaniline (7.37 g, 26.28 mmol)and triethyl methanetricarboxylate (6.40 mL, 30.42 mmol) were mixedtogether in diglyme (30 mL). The mixture was heated at 160° C. overnightand the diglyme was removed. The residue was purified by columnchromatography using EtOAc/hexanes (gradient 0-50%). After concentrationof the desired fractions, the residue was triturated with hexanes andthe solid was filtered to afford ethyl1-benzyl-6-(4-(dimethylamino)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(4.34 g, 35%) over 2 steps.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 0.94 (t, J=7.4 Hz, 3H) 1.47 (t, J=7.1Hz, 3H) 2.18 (q, J=7.4 Hz, 2H) 2.99 (s, 6H) 4.49 (q, J=7.1 Hz, 2H) 5.04(br. s., 2H) 6.61 (d, J=8.5 Hz, 2H) 6.81 (d, J=8.5 Hz, 2H) 6.85-6.90 (m,2H) 7.09-7.22 (m, 3H) 13.83 (s, 1H). LC-MS 419.2 [M−H]⁻, 421.4 [M+H]⁺,RT 1.62 min.

Step 3

The product ethyl1-benzyl-6-(4-(dimethylamino)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.50 g, 1.19 mmol) obtained above was dissolved in THF (8 mL). Amixture of MeOH (80 μL, 1.98 mmol) and PPh₃ (0.47 g, 1.79 mmol) wereadded. The mixture was cooled to 0° C., then DIAD (0.35 mL, 1.77 mmol)was added dropwise. The reaction was stirred at 0° C. for 15 min andslowly allowed to warm to room temperature. After 30 min, the startingmaterial was no longer detected by LC/MS. The THF was concentrated andthe residue was purified by column chromatography using EtOAc/hexanes(gradient 0-50%). The product was obtained as an oil (˜0.74 g)contaminated with an inseparable DIAD by-product.

The obtained product was dissolved in MeOH (6 mL) and treated with aLiOH solution (1M H₂O, 6.0 mL, 6.0 mmol). The mixture was microwaved for60 min at 120° C., then cooled to room temperature and a solid wasfiltered off. The MeOH from the mother liquor was removed under reducedpressure, then the aqueous phase was diluted with H₂O (15 mL) andextracted with EtOAc (10 mL). The organic phase was discarded and theaqueous phase was acidified with 1M HCl to pH˜3. A yellow solid wasfiltered off, then washed with H₂O and dried to afford1-benzyl-6-(4-(dimethylamino)phenyl)-5-ethyl-4-methoxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (0.25 g, 52%) over 2 steps.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 0.93 (t, J=7.4 Hz, 3H) 2.22 (q, J=7.4Hz, 2H) 3.01 (s, 6H) 4.16 (s, 3H) 5.13 (br. s., 2H) 6.64 (d, J=8.8 Hz,2H) 6.84 (d, J=8.8 Hz, 2H) 6.87-6.91 (m, 2H) 7.20-7.26 (m, 3H). LC-MS405.3 [M−H]⁻, 407.4 [M+H]⁺, RT 1.48 min.

Step 4

A suspension of1-benzyl-6-(4-(dimethylamino)phenyl)-5-ethyl-4-methoxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (71.2 mg, 0.18 mmol) in a mixture of MeOH (1.5 mL) and AcOH (1.5mL) was hydrogenated in a Paar shaker under 65 psi of H₂ for 6 h. Aftercomplete consumption of starting material was observed, DCM was added tothe mixture, then the catalyst was filtered off and the filtrate waswashed with DCM. The mother liquor was concentrated and the residue wastriturated with Et₂O to afford6-(4-(dimethylamino)phenyl)-5-ethyl-4-methoxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (33 mg, 60%) as yellow solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.15 (t, J=7.4 Hz, 3H) 2.55 (q, J=7.4Hz, 2H) 4.13 (s, 3H) 6.82 (d, J=8.5 Hz, 2H) 7.34 (d, J=8.5 Hz, 2H) 11.55(br. s., 1H) 14.42 (br. s., 1H). LC-MS 315.3 [M−H]⁻, 317.2 [M+H]⁺, RT1.10 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 2996-{4-[di(prop-2-en-1-yl)amino]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.6 Hz, 3H) 2.64 (q, J= 7.6 Hz, 2H) 4.03 (br. s., 4H) 5.17-5.29 (m, 4H) 5.82-5.95 (m, 2H) 6.80(d, J = 8.8 Hz, 2H) 7.33 (d, J = 8.8 Hz, 2H) 8.52 (s, 1H) 11.86 (br. s.,1H) 13.41 (br. s, 1H). LC-MS 337.9 [M − H]⁻, 339.9 [M + H]⁺, RT 1.33min. 3006-{4-[di(prop-2-en-1-yl)amino]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J = 7.4 Hz,3H) 2.36 (q, J = 7.4 Hz, 2H) 4.01 (d, J = 4.9 Hz, 4H) 5.12-5.21 (m, 4H)5.87 (ddd, J = 12.5, 10.1, 4.9 Hz, 2H) 6.77 (d, J = 8.8 Hz, 2H) 7.26 (d,J = 8.8 Hz, 2H) 12.51 (br. s., 1H) 13.85 (br. s., 1H). LC-MS 352.6 [M −H]⁻, 354.9 [M + H]⁺, RT 1.49 min.

EXAMPLE 196-[4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 301) Step 1

To a solution of methyl6-(4-(diallylamino)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.116 g, 0.33 mmol) in DCM (3 mL) was added a Grubbs-II catalyst (14mg, 5 mol %). The reaction mixture was stirred at room temperatureovernight and then diluted with Et₂O (˜5 ml). The resulting yellowprecipitate was filtered and washed with Et₂O to afford methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.075 g, 71%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.17 (t, J=7.6 Hz, 3H) 2.54 (q, J=7.6Hz, 2H) 3.94 (s, 3H) 4.18 (s, 4H) 6.00 (s, 2H) 6.60 (d, J=8.8 Hz, 2H)7.33 (d, J=8.8 Hz, 2H) 8.24 (s, 1H) 9.02 (br. s., 1H). LC-MS 325.0[M+H]⁺, RT 1.22 min.

Step 2

A mixture of methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(37.4 mg, 0.12 mmol) and LiOH (1M aqueous, 0.40 mL, 0.40 mmol) in THF(0.80 mL) was heated at 50° C. for 2 h. The reaction mixture was cooledto room temperature and acidified with 1M HCl to pH˜2. A bright yellowprecipitate was filtered off, then washed with H₂O and Et₂O and dried toafford6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (25.0 mg, 70%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.06 (t, J=7.3 Hz, 3H) 2.48 (q, J=7.3Hz, 2H) 4.13 (s, 4H) 6.06 (s, 2H) 6.64 (d, J=8.5 Hz, 2H) 7.35 (d, J=8.5Hz, 2H) 8.31 (s, 1H) 13.05 (br. s., 1H) 15.04 (s, 1H). LC-MS 308.7[M−H]⁻, 311.0 [M+H]⁺, RT 1.22 min.

EXAMPLE 206-[4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 302) Step 1

To a solution of methyl6-(4-(diallylamino)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.188 g, 0.51 mmol) in DCM (6 mL) was added a Grubbs-II catalyst (22mg, 5 mol %). The reaction mixture was stirred at room temperatureovernight. A yellow precipitate was filtered and washed with Et₂O toafford methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.137 g, 79%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.02 (t, J=7.3 Hz, 3H) 2.31 (q, J=7.3Hz, 2H) 3.84 (s, 3H) 4.11 (s, 4H) 6.05 (s, 2H) 6.59 (d, J=8.5 Hz, 2H)7.26 (d, J=8.5 Hz, 2H) 11.23 (s, 1H) 13.56 (s, 1H). LC-MS 341.1 [M+H]⁺,RT 1.41 min.

Step 2

A mixture of methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(41.6 mg, 0.12 mmol) and LiI (41.0 mg, 0.31 mmol) in EtOAc (1.5 mL) washeated at 65° C. for 2 h. After the mixture was cooled to roomtemperature, Et₂O (5 mL) and 1 M HCl (2 mL) were added. A yellowprecipitate was filtered off and then washed with H₂O and Et₂O. Afterdrying, the product6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (25.8 mg, 66%) was obtained.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (t, J=7.3 Hz, 3H) 2.38 (q, J=7.3Hz, 2H) 4.13 (s, 4H) 6.06 (s, 2H) 6.64 (d, J=8.8 Hz, 2H) 7.32 (d, J=8.8Hz, 2H) 12.58 (br. s., 1H) 13.84 (br. s., 1H). LC-MS 324.7 [M−H]⁻, 326.9[M+H]⁺, RT 1.41 min.

EXAMPLE 216-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 303) Step 1

To a suspension of methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.112 mg, 0.35 mmol) in THF was added NMO (40 mg, 0.14 mmol) followedby an OsO₄ solution (4% aqueous, 50 μL, 2.5 mol %). The reaction mixturewas stirred at room temperature and monitored by LC/MS. After completeconversion to the product (˜10 h), the precipitate was filtered off,washed with 10% aqueous Na₂S₂O₃ and H₂O then Et₂O. After drying, theproduct methyl6-(4-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.099 g, 80%) was obtained.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.01 (t, J=7.4 Hz, 3H) 2.37 (q, J=7.4Hz, 2H) 3.15 (dd, J=9.6, 3.9 Hz, 2H) 3.45 (dd, J=9.6, 5.0 Hz, 2H) 3.74(s, 3H) 4.16 (br. s., 2H) 4.96 (br. s., 2H) 6.54 (d, J=8.5 Hz, 2H) 7.23(d, J=8.5 Hz, 2H) 8.02 (s, 1H) 11.76 (br. s., 1H). LC-MS 359.2 [M+H]⁺,RT 0.86 min.

Step 2

The product6-(4-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(52.3 mg, 0.15 mmol) obtained above was dissolved in THF (1.0 mL) andtreated with a LiOH solution (1M aqueous, 0.50 mL, 0.50 mmol) at 50° C.for 4 h. The mixture was cooled to room temperature and acidified with 1M HCl to pH˜2. A yellow precipitate was filtered off and washed with H₂Oand Et₂O. After drying, the product6-(4-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (37.2 mg, 74%) was obtained.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J=7.4 Hz, 3H) 2.05-2.33 (m, 3H)2.44-2.55 (m, 1H) 2.58 (q, J=7.4 Hz, 2H) 3.46 (dd, J=9.5, 7.2 Hz, 0H)3.83 (t, J=9.5 Hz, 0H) 5.18 (d, J=7.2 Hz, 1H) 6.72 (d, J=8.8 Hz, 2H)7.26 (d, J=3.5 Hz, 1H) 7.33 (d, J=8.8 Hz, 2H) 7.80 (d, J=3.5 Hz, 1H)8.49 (s, 1H) 12.29 (br. s., 1H) 13.74 (s, 1H). LC-MS 342.8 [M−H]⁻, 345.1[M+H]⁺, RT 0.86 min.

EXAMPLE 226-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 304)

To a suspension of methyl6-(4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(52.8 mg, 0.16 mmol) in THF was added NMO (20 mg, 0.17 mmol), followedby an 050₄ solution (4% aqueous, 50 μL, 5 mol %). The reaction mixturewas stirred at room temperature and reaction completion was monitored byLC/MS. After complete conversion to the product (˜4 days), theprecipitate was filtered off, then washed with 10% aqueous Na₂S₂O₃, H₂Oand Et₂O. After drying, the product (˜40 mg) was suspended in EtOAc (1.5mL) and treated with LiI (36.0 mg, 0.27 mmol) at 75° C. for 2 h. Afterthe reaction mixture was cooled to room temperature, Et₂O (5 mL) and 1 MHCl (2 mL) were added. The resulting yellow precipitate was filteredoff, then washed with H₂O and Et₂O and dried to afford6-(4-((3R,4S)-3,4-dihydroxypyrrolidin-1-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (21.9 mg, 39%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.03 (t, J=7.3 Hz, 3H) 2.38 (q, J=7.3Hz, 2H) 3.16 (dd, J=9.6, 3.9 Hz, 2H) 3.46 (dd, J=9.6, 5.4 Hz, 2H)4.14-4.20 (m, 2H) 6.58 (d, J=8.5 Hz, 2H) 7.27 (d, J=8.5 Hz, 2H) 12.57(s, 1H) 13.83 (s, 1H). LC-MS 359.1 [M−H]⁻, 361.1 [M+H]⁺, RT 1.00 min.

EXAMPLE 236-[5-(dimethylamino)thiophen-2-yl]-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 305) Step 1: 1-(5-(dimethylamino)thiophen-2-yl)butan-1-one

A mixture of 1-(5-bromothiophen-2-yl)butan-1-one (2.50 g, 10.72 mmol)and a solution of Me₂NH (40% aqueous, 6.0 mL) was heated at 100° C. in asealed vial over 48 hrs. After the mixture was cooled to roomtemperature, the mixture was diluted with H₂O and the product wasextracted with DCM (3×40 mL). The organic phase was dried over Na₂SO₄,then the solvent was removed and the residue was purified by columnchromatography using EtOAc/hexanes (gradient 0-50%) to afford theproduct 1-(5-(dimethylamino)thiophen-2-yl)butan-1-one (2.00 g, 94%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 0.98 (t, J=7.4 Hz, 3H) 1.75 (sxt, J=7.4Hz, 2H) 2.70 (t, J=7.4 Hz, 2H) 3.05 (s, 6H) 5.83 (d, J=4.4 Hz, 1H) 7.46(d, J=4.4 Hz, 1H). LC-MS 198.0 [M+H]⁺, RT 1.11 min.

Step 2

To a solution of methyl1-(2,4-dimethoxybenzyl)-6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.916 g, 2.00 mmol) in DCM (6 mL) was added anisole (0.50 mL) followedby TFA (1.0 mL). The reaction mixture was stirred at room temperaturefor 1 h until complete consumption of the starting material wasobserved. The solvents were removed and the residue was purified bycolumn chromatography using EtOAc/hexanes (gradient 50-100%) to affordmethyl6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.188 g, 31%) as a solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.32 (t, J=7.5 Hz, 3H) 2.82 (q, J=7.5Hz, 2H) 3.05 (s, 6H) 3.95 (s, 3H) 5.90 (d, J=4.4 Hz, 1H) 7.39 (d, J=4.4Hz, 1H) 7.93 (s, 1H) 11.05 (br. s., 1H). LC-MS 307.1 [M+H]⁺, RT 1.21min.

Step 3

To a suspension of methyl6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.188 g, 0.61 mmol) in THF (3.5 mL) was added a LiOH solution (1Maqueous, 1.8 mL, 1.8 mmol). The reaction was heated at 65° C. for 4 h.After the mixture was cooled to room temperature, the mixture wasacidified with 1M HCl to pH˜2. A solid was filtered off, then washedwith H₂O and Et₂O and dried to afford6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (0.123 g, 69%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.16 (t, J=7.4 Hz, 3H) 2.73 (q, J=7.4Hz, 2H) 3.01 (s, 6H) 6.11 (d, J=4.4 Hz, 1H) 7.57 (d, J=4.4 Hz, 1H) 8.13(s, 1H) 12.57 (br. s., 1H) 14.75 (br. s., 1H). LC-MS 291.0 [M−H]⁻, 293.0[M+H]⁺, RT 1.06 min.

EXAMPLE 246-[5-(dimethylamino)thiophen-2-yl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 306) Step 1

To a solution of methyl1-(2,4-dimethoxybenzyl)-6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.224 g, 0.47 mmol) in DCM (2 mL) was added anisole (0.50 mL) followedby TFA (0.50 mL). The reaction mixture was stirred at room temperaturefor 2 h until complete consumption of the starting material wasobserved. The solvents were removed and the residue was partitionedbetween DCM and NaHCO₃ (aqueous saturated). The organic phase was driedover Na₂SO₄ and the solvents were removed. The residue was trituratedwith Et₂O, then the solid was filtered and washed with Et₂O to providemethyl6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.075 g, 49%). LC-MS 322.8 [M+H]⁺, RT 1.20 min.

Step 2

Methyl6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(70 mg, 0.22 mmol) was suspended in EtOAc (1.5 mL) and treated with LiI(73.0 mg, 0.54 mmol) at 65° C. for 2 h. After the mixture was cooled toroom temperature, Et₂O (5 mL) and 1 M HCl (2 mL) were added. Theresulting yellow precipitate was filtered, then washed with H₂O and Et₂Oand dried to afford6-(5-(dimethylamino)thiophen-2-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (48.5 mg, 72%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.12 (t, J=7.4 Hz, 3H) 2.67 (d, J=7.4Hz, 2H) 3.00 (s, 6H) 6.09 (d, J=4.4 Hz, 1H) 7.46 (d, J=4.4 Hz, 1H) 12.19(br. s., 1H) 13.78 (br. s., 1H). LC-MS 307.1 [M−H]⁻, 309.0 [M+H]⁺, RT1.26 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 3075-ethyl-4-hydroxy-2-oxo-6-[5-(pyrrolidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.23 (t, J = 7.4 Hz, 3H)2.09-2.13 (m, 4H) 2.78 (q, J = 7.4 Hz, 2H) 3.28-3.41 (m, 4H) 5.87 (d, J= 4.4 Hz, 1H) 7.30 (d, J = 4.4 Hz, 1H) 10.37 (br. s., 1H) 13.67 (s, 1H)14.85 (s, 1H). LC-MS 333.1 [M − H]⁻, 335.0 [M + H]⁺, RT 1.38 mm. 3085-ethyl-2-oxo-6-[5-(piperidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylicacid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.15 (t, J = 7.4 Hz, 3H) 1.52-1.60(m, 2H) 1.60-1.68 (m, 4H) 2.72 (q, J = 7.4 Hz, 2H) 3.22-3.28 (m, 4H)6.31 (d, J = 4.1 Hz, 1H) 7.53 (d, J = 4.1 Hz, 1H) 8.17 (s, 1H) 12.63(br. s., 1H) 14.75 (br. s., 1H). LC-MS 331.0 [M − H]⁻, 333.0 [M + H]⁺,RT 1.25 min. 3095-ethyl-4-hydroxy-2-oxo-6-[5-(piperidin-1-yl)thiophen-2-yl]-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.22 (t, J = 7.4 Hz, 3H)1.62-1.69 (m, 2H) 1.76-1.86 (m, 4H) 2.75 (q, J = 7.4 Hz, 2H) 3.28-3.35(m, 4H) 6.28 (d, J = 4.4 Hz, 1H) 7.24 (d, J = 4.4 Hz, 1H) 10.22 (br. s.,1H) 13.75 (s, 1H) 14.64 (br. s., 1H). LC-MS 347.1 [M − H]⁻, 349.1 [M +H]⁺, RT 1.44 min.

EXAMPLE 256-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid(Cpd 310) Step 1

A mixture of 6-1-(4-(dimethylamino)phenyl)ethanone (1.059 g, 6.49 mmol)and DMF-DMA (3.50 mL, 26.31 mmol) was microwaved at 200° C. for 40 min.The mixture was cooled to room temperature. A precipitate was formed,collected by filtration and washed with Et₂O to provide3-(dimethylamino)-1-(4-(dimethylamino)phenyl)prop-2-en-1-one (1.180 g,83%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 3.33 (s, 12H) 5.77 (d, J=12.6 Hz, 1H)6.68 (d, J=9.1 Hz, 2H) 7.58 (d, J=12.6 Hz, 1H) 7.77 (d, J=9.1 Hz, 2H).

Step 2

To a suspension of NaH (60% oil, 0.54 g, 13.50 mmol) in DMF (10 mL) wasadded a solution of3-(dimethylamino)-1-(4-(dimethylamino)phenyl)prop-2-en-1-one (1.18 g,5.41 mmol), cyanoacetamide (0.50 g, 5.94 mmol) and MeOH (0.55 mL, 13.60mmol) in DMF (10 mL). The reaction mixture was stirred at roomtemperature for 15 min and then heated to 95° C. overnight. The mixturewas cooled to room temperature and the reaction was quenched with NH₄Cl(aqueous saturated). The resulting orange precipitate was filtered off,then washed several times with H₂O, dried in an N₂-flow and washed withEt₂O. The product6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile(1.05 g, 81%) was obtained.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 3.00 (s, 6H) 6.65 (d, J=7.9 Hz, 1H) 6.77(d, J=8.8 Hz, 2H) 7.73 (d, J=8.8 Hz, 2H) 8.02 (d, J=7.9 Hz, 1H) 12.25(br. s., 1H). LC-MS 240.1 [M+H]⁺, RT 1.12 min.

Step 3

6-(4-(dimethylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile(0.304 g, 1.17 mmol) was heated with 6M HCl (10 mL) at 100° C.overnight. The HCl was concentrated under reduced pressure and 1M NaOHwas added to the residue. The insoluble material was filtered off byvigorous shaking of the mixture. The mother liquor was acidified with 1MHCl to pH˜1. After the mixture was cooled to room temperature, aprecipitate formed that was collected by filtration and washed withwater. After drying, the product (0.195 g, 60%) was obtained in 91%purity.

¹H NMR (500 MHz, DMSO-d₆) δ ppm 3.02 (s, 6H) 6.80 (d, J=9.1 Hz, 2H) 6.96(d, J=7.9 Hz, 1H) 7.79 (d, J=9.1 Hz, 2H) 8.27 (d, J=7.9 Hz, 1H) 13.02(br. s., 1H) 14.75 (br. s., 1H). LC-MS 256.9 [M−H]⁻, 259.2 [IVI+H]⁺, RT1.12 min.

EXAMPLE 266-(4-(tert-butoxy)phenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 311)

Methyl 6-(4-bromophenyl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylate(0.106 g, 0.31 mmol), Pd-catalyst (7.3 mg, 5 mol %) and t-BuONa (0.160g, 1.66 mmol) were mixed under Argon in a heat-gun dried vial. Anhydroustoluene (1.0 mL) was added and the reaction mixture was heated underArgon at 80° C. for 1 h. The reaction was cooled to room temperature andTHF (1.5 mL) and LiOH (1M aqueous, 1 mL) were added. The mixture washeated overnight at 50° C., then cooled to room temperature andacidified with 1M HCl to pH˜2. The product was extracted with DCM (3×7mL) and the organic phase was dried over Na₂SO₄. The solvents wereconcentrated and the residue was purified by preparative HPLC to affordthe product (0.012 g, 12%) as a white solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.18 (t, J=7.6 Hz, 3H) 1.47 (s, 9H) 2.57(q, J=7.6 Hz, 2H) 7.17 (d, J=8.5 Hz, 2H) 7.39 (d, J=8.5 Hz, 2H) 8.55 (s,1H) 12.28 (br. s., 1H) 13.62 (br. s., 1H). LC-MS 314.0 [M−H]⁻, 316.2[IVI+H]⁺, RT 1.49 min.

EXAMPLE 276-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylicacid (Cpd 327) Step 1: benzyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

A mixture of methyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.656 g, 2.0 mmol), prepared according to the procedure in Example 2,in benzyl alcohol (2.1 mL, 20 mmol) was heated at 150° C. After 1 h, themixture was diluted with ether, then filtered and washed with ether togive the title compound as a yellow solid (0.83 g, 98%). LC-MS 405.2[M+H]⁺, RT 1.55 min.

Step 2: benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylate

To a suspension of benzyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(404 mg, 1.0 mmol) in dioxane/water (20 mL, 3/1 v/v) were added asolution of OSO₄ (0.32 mL, 0.05 mmol, 4% in water), 2,6-lutidine (0.23mL, 2.0 mmol) and NaIO₄ (0.62 g, 3.0 mmol). After 5 h, the mixture wasdiluted with EtOAc, then filtered and washed with EtOAc. The filtratewas concentrated and chromatographed with 0-2.5% MeOH/CH₂Cl₂ to give thetitle compound as a yellow foam (220 mg, 50%). LC-MS 407.2 [M+H]⁺, RT1.23 min.

Step 3:6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylicacid

A mixture of benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylate(40 mg, 0.1 mmol) and 10% Pd/C (10 mg) in THF (1 mL) and MeOH (3 mL) wasstirred vigorously under H₂ (1 atm). After 1 h, the mixture was filteredthrough Celite, then washed with 20% MeOH/CH₂Cl₂. The filtrate wasconcentrated and washed with CH₃CN to give the title compound as ayellow solid (20 mg, 63%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.98 (s, 6H), 3.15 (s, 2H), 6.79 (d,J=9.1 Hz, 2H), 7.48 (d, J=9.1 Hz, 2H), 12.39-12.65 (m, 1H), 13.77-14.08(br s, 1H), 16.02-16.34 (br s, 1H). LC-MS 317.2 [M+H]⁺, RT 1.13 min.

EXAMPLE 286-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 328) Step 1: benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

To a suspension of benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylate(83 mg, 0.2 mmol) in THF (1 mL) and EtOH (1 mL) was added NaBH₄. After10 min, the reaction was quenched with 6 N HCl (0.2 mL), thenconcentrated and chromatographed with 0-10% MeOH/CH₂Cl₂ to give thetitle compound as a yellow foam (35 mg, 38%). LC-MS 409.3 [M+H]⁺, RT1.24 min.

Step 2:6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Following the procedure in Example 27, Step 3, benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylate(35 mg, 0.085 mmol), 10% Pd/C (10 mg) in THF (1 mL) and MeOH (2 mL) werereacted under H₂ (1 atm) to afford the title compound as a yellow foam(22 mg, 81%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.56 (t, J=7.3 Hz, 2H), 2.99 (s, 6H),3.44-3.51 (m, 2H), 6.80 (d, J=8.8 Hz, 2H), 7.39 (d, J=9.1 Hz, 2H),12.53-12.61 (br s, 1H), 13.83-13.89 (br s, 1H), 16.26-16.35 (br s, 1H).LC-MS 319.1 [M+H]⁺, RT 1.03 min.

EXAMPLE 295-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 329) Step 1: benzyl5-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

To a solution of benzyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(81 mg, 0.2 mmol) in THF/t-BuOH (2 mL, 7/1 v/v) was added a solution of050₄ (95 mt, 0.015 mmol, 4% in water) and NMO (70 mg, 0.6 mmol). Themixture was stirred at room temperature for 15 h, then concentrated andchromatographed with 0-5% MeOH/CH₂Cl₂ to give the title compound as ayellow foam (86 mg, 99%). LC-MS 439.2 [M+H]⁺, RT 1.13 min.

Step 2:5-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Following the procedure in Example 27, Step 3, benzyl5-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(70 mg, 0.16 mmol), 10% Pd/C (20 mg) in THF (2 mL) under H₂ (1 atm) werereacted to afford the title compound as a yellow foam (53 mg, 95%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.37-2.47 (m, 2H), 2.97 (s, 6H),3.15-3.21 (m, 2H), 3.72-3.80 (m, 1H), 4.40-4.47 (m, 1H), 4.60-4.69 (m,1H), 6.76 (d, J=7.9 Hz, 2H), 7.46 (d, J=8.5 Hz, 2H). LC-MS 349.2 [M+H]⁺,RT 0.97 min.

EXAMPLE 30E)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylicacid (Cpd 330) Step 1: (E)-methyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylate

A mixture of methyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(492 mg, 1.5 mmol), prepared according to the procedure of Example 2,and PdCl₂(CH₃CN)₂ (39 mg, 0.15 mmol) in CH₂Cl₂ was refluxed for 30 min.The mixture was filtered through Celite. The filtrate was concentratedand chromatographed with 0-2% MeOH/CH₂Cl₂ to give the title compound asan orange solid (0.31 g, 63%). LC-MS 329.2 [M+H]⁺, RT 1.23 min.

Step 2:(E)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylicacid

A mixture of (E)-methyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylate(66 mg, 0.2 mmol) and LiI (134 mg, 1.0 mmol) in EtOAc (2 mL) was heatedat 65° C. After 3 h, the mixture was treated with 1 N HCl (1 mL). Theresulting solid was filtered, then washed with water and CH₃CN, anddried to give the title compound as a yellow solid (37 mg, 60%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.72 (dd, J=6.6, 1.6 Hz, 3H), 3.00 (s,6H), 5.84-5.92 (m, 1H), 6.19-6.28 (m, 1H), 6.80 (d, J=8.8 Hz, 2H), 7.32(d, J=9.1 Hz, 2H), 12.61-12.70 (br s, 1H), 14.29-14.35 (br s, 1H),16.25-16.40 (br s, 1H). LC-MS 315.1 [M+H]⁺, RT 1.29 min.

EXAMPLE 316-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 331) Step 1: (E)-benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylate

Following the procedure of Example 30, Step 1, benzyl5-allyl-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.97 g, 2.5 mmol) and PdCl₂(CH₃CN)₂ (90 mg, 0.25 mmol) in CH₂Cl₂ (25mL) were reacted to give the title compound as a yellow solid (0.80 g,80%). LC-MS 405.3 [M+H]⁺, RT 0.90 min.

Step 2: benzyl6-(4-(dimethylamino)phenyl)-5-formyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

Following the procedure of Example 27, Step 2, (E)-benzyl6-(4-(dimethylamino)phenyl)-4hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylate (0.30 g,0.74 mmol), OSO₄ (0.74 mL, 0.074 mmol, 2.5% in t-BuOH), 2,6-lutidine(0.19 mL, 1.6 mmol) and NaIO₄ (0.35 g, 1.6 mmol) in dioxane/water (20mL, 3/1 v/v) were reacted to give the title compound as a yellow solid(0.243 g, 83%). LC-MS 393.2 [M+H]⁺, RT 0.74 min.

Step 3: benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

Following the procedure in Example 28, Step 1, benzyl6-(4-(dimethylamino)phenyl)-5-formyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(60 mg, 0.15 mmol) and NaBH₄ (7.6 mg, 0.2 mmol) in EtOH (2 mL) and THF(2 mL) were reacted to give the title compound as a yellow solid (39 mg,67%). LC-MS 395.2 [M+H]⁺, RT 0.67 min.

Step 4:6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Following the procedure in Example 2, Step 3, benzyl6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylate(39 mg, 0.1 mmol), 10% Pd/C (8 mg) in 10% MeOH/CH₂Cl₂ (2 mL) under H₂ (1atm) were reacted to give the title compound as a yellow solid (26 mg,86%). LC-MS 305.1 [M+H]⁺, RT 0.56 min.

EXAMPLE 326-(4-(dimethylamino)phenyl)-4-hydroxy-5-(methoxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 332) Step 1: benzyl2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-formylnicotinate

To a mixture of benzyl6-(4-(dimethylamino)phenyl)-5-formyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(627 mg, 1.6 mmol), benzyl alcohol (0.36 mL, 3.52 mmol) and triphenylphosphine (0.92 g, 3.52 mmol) in THF (16 mL) at 0° C. was added DIADdropwise. After the addition, the mixture was stirred at roomtemperature for 15 h. The mixture was then concentrated andchromatographed with 0-30% EtOAc in hexanes to give the title compoundas a yellow oil (0.19 g, 21%). LC-MS 573.3 [M+H]⁺, RT 0.95 min.

Step 2: benzyl2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-(hydroxymethyl)nicotinate

Following the procedure in Example 28, Step 1,2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-formylnicotinate (0.19g, 0.33 mmol) and NaBH₄ (25 mg, 0.66 mmol) in EtOH (1 mL) and THF (1 mL)were reacted to give the title compound as a light yellow oil (0.172 g,90%). LC-MS 575.4 [M+H]⁺, RT 1.00 min

Step 3: benzyl2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-(methoxymethyl)nicotinate

To a solution of benzyl2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-(hydroxymethyl)nicotinate (0.172 g, 0.3 mmol) and MeI (0.5 mL, 8 mmol) in THF (5 mL) atroom temperature was added a NaH solution (24 mg, 0.6 mmol, 60% inmineral oil). After 15 h, the reaction was quenched with water andextracted with EtOAc. The organics were concentrated and chromatographedwith 0-10% EtOAc in hexanes to give the title compound as a yellow oil(60 mg, 30%). LC-MS 589.3 [M+H]⁺, RT 1.08 min.

Step 4:6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(methoxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Following the procedure in Example 27, Step 3, benzyl2,4-bis(benzyloxy)-6-(4-(dimethylamino)phenyl)-5-(methoxymethyl)nicotinate(60 mg, 0.1 mmol), 10% Pd/C (8 mg) in 10% MeOH/CH₂Cl₂ (2 mL) under H₂ (1atm) were reacted to give the title compound as a yellow solid (17 mg,53%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 3.01 (s, 6H), 3.28 (s, 3H), 4.05-4.09(s, 2H), 6.82 (d, J=9.2 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 12.59-12.67 (brs, 1H), 13.76-13.86 (br s, 1H), 15.87-15.98 (br s, 1H). LC-MS 317.2[M+H]⁺, RT 0.70 min.

EXAMPLE 336-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylicacid (Cpd 333) Step 1:1-(2,4-dimethoxybenzyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylicacid

To a solution of1-(2,4-dimethoxybenzyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-((trimethylsilyl)ethynyl)-1,2-dihydropyridine-3-carboxylicacid (27 mg, 0.05 mmol), prepared according to the procedures in Example2, in dioxane (0.5 mL) was added TMSOK (28 mg, 0.2 mmol). After heatingat 50° C. for 4 h, the reaction mixture was acidified with 1N HCl to pH3-4 and concentrated. The residue was chromatographed with 0-3%MeOH/CH₂Cl₂ to give the title compound as a yellow solid (13 mg, 56%).LC-MS 463.2 [M+H]⁺, RT 0.81 min.

Step 2:6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylicacid

To the product1-(2,4-dimethoxybenzyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylicacid (12 mg, 0.026 mmol) obtained above was added i-Pr₃SiH (0.30 mL)followed by TFA (0.60 mL). The mixture was heated at 50° C. for 15 minuntil complete consumption of starting material was observed. The TFAwas removed under reduced pressure, followed by treatment with 1 N HClin ether (1 mL) to give the title compound as a yellow solid (9 mg, 77%,HCl salt).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 2.42 (s, 3H), 3.04 (s, 6H), 6.74 (s,1H), 6.86 (d, J=9.1 Hz, 2H), 7.67 (d, J=9.1 Hz, 2H), 13.02-13.11 (br s,1H). LC-MS 313.2 [M+H]⁺, RT 0.62 min.

EXAMPLE 345-ethyl-4-hydroxy-6-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 334) Step 1: 6-chloro-5-ethyl-4-hydroxypyridin-2(1H)-one

A mixture of butyronitrile (30 mL) and malonyl dichloride (25.0 g, 177mmol) was stirred at room temperature under N₂ for 3 days. The reactionmixture was diluted with dioxane (100 mL) and filtered. The precipitatewas washed with dioxane (20 mL), then ethyl ether (2×30 mL) and dried inair to provide 6-chloro-5-ethyl-4-hydroxypyridin-2(1H)-one (12.7 g, 67%pure, containing 33% of a 6-chloro-2-propyl-1,2-dihydropyrimidin-4-olby-product, based on ¹HNMR) which was used directly in the next stepwithout further purification.

¹H NMR (500 MHz, MeOH-d₄) δ ppm 6.43 (1H, s), 2.72 (2H, q, J=7.36 Hz),1.09-1.19 (3H, m).

Step 2: 4,6-bis(benzyloxy)-2-chloro-3-ethylpyridine

The intermediate obtained in Step 1 (12.7 g) was dissolved in THF (250mL) followed by the addition of Ph₃P (54.0 g, 210 mmol). The mixture wascooled in an ice-water bath and DIAD (42 mL, 211 mmol) was addeddropwise. After the addition, the reaction mixture was stirred for 5min, followed by the addition of benzyl alcohol (23.6 mL, 228 mmol)dropwise. The cooling bath was removed and the mixture was stirred foranother 4 hr. The solvents were removed on a rotovap. The residue wastreated with a 1:1 mixture of hexanes and ethyl ether (600 mL) andstirred for 0.5 hr. The precipitate was filtered and washed with the 1:1mixture of hexanes and ethyl ether until the desired product was notfound in the wash. All the filtrates were combined, then concentratedand chromatographed (silica gel, ethyl acetate in hexanes 0-3% gradient)to furnish an intermediate, 4,6-bis(benzyloxy)-2-chloro-3-ethylpyridine,as a colorless oil (7.7 g, yield: 12.3%, two steps).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 7.28-7.56 (10H, m), 6.27 (1H, s),5.30-5.39 (2H, m), 5.08 (2H, s), 2.75 (2H, q, J=7.25 Hz), 1.08-1.19 (3H,m).

Step 3: benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate

To a solution of the intermediate obtained in Step 2 (7.7 g, 21.8 mmol)in THF (80 mL), at −78° C., was added n-BuLi (21.8 mL, 54.4 mmol)dropwise. The mixture was stirred for an additional 15 min at −78° C.Benzyl chloroformate (4.7 mL, 32.6 mmol) was then added and theresulting mixture was stirred for 10 min before the cooling bath wasremoved. The mixture was allowed to warm to room temperature whilestirring. The reaction was quenched with a solution of NH₄Cl (5 mL),diluted with ethyl ether (150 mL), then washed with water (2×30 mL) andbrine (30 mL). After drying with Na₂SO₄, the solvent was removed and theresidue was chromatographed (silica gel, ethyl acetate in hexanes, 0-5%)to provide the product as a white crystalline material (6.9 g, 65%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 7.24-7.43 (15H, m), 5.39 (2H, s), 5.30(2H, s), 4.97 (2H, s), 2.66 (2H, q, J=7.57 Hz), 1.10 (3H, t, J=7.41 Hz).

Step 4: benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(4-hydroxyphenyl)nicotinate

A mixture of benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate (83mg, 0.17 mmol), 4-hydroxyphenylboronic acid (35 mg, 0.26 mmol),Pd₂(dba)₃ (7.8 mg, 0.0085 mmol), tri-tert-butylphosphoniumtetrafluoroborate (4.9 mg, 0.017 mmol) and KF (100 mg, 1.7 mmol) in THF(2.0 mL) was stirred at 60° C. overnight under an Argon atmosphere, thenfiltered through Celite. The solvent was evaporated and the residuepurified with silica column chromatography using ethyl acetate inhexanes (2-30%) to give the product benzyl2,4-bis(benzyloxy)-5-ethyl-6-(4-hydroxyphenyl)nicotinate (69 mg, 74%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.03 (d, J=7.3 Hz, 3H), 2.57 (d, J=7.6Hz, 2H), 4.86-5.02 (br s, 1H), 5.03 (s, 2H), 5.34 (s, 2H), 5.43 (s, 2H),6.86-6.91 (m, 2H), 7.27-7.42 (m, 17H). LC-MS 546.3 [M+H]⁺, RT 1.69 min.

Step 5:5-ethyl-4-hydroxy-6-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid

A solution of benzyl2,4-bis(benzyloxy)-5-ethyl-6-(4-hydroxyphenyl)nicotinate (69 mg, 0.13mmol) in a 3:1 mixture of ethyl acetate/methanol (2.0 mL) washydrogenated with 10% Pd/C (20 mg) under H₂ for 1 h at room temperature.The mixture was filtered through Celite, the solvents were evaporatedand the solid was triturated with ether to give the title compound (27mg, 77%).

¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.00 (t, J=7.4 Hz, 3H), 2.32 (d, J=7.3Hz, 2H), 6.87-6.92 (m, 2H), 7.27-7.32 (m, 2H), 9.99 (s, 1H), 12.48-12.75(m, 1H), 13.77-14.03 (m, 1H), 16.13-16.43 (m, 1H). LC-MS 274.2 [M−H]⁻,276.1 [M+H]⁺, RT 1.11 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and include compoundsselected from:

Cpd Name 3356-(6-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04(3 H, t, J = 7.41 Hz), 1.92-2.04 (1 H, m), 2.24-2.34 (1 H, m), 2.34-2.42(2 H, m), 3.33 (6 H, s, obscured by water), 3.36-3.45 (2 H, m),3.63-3.70 (1 H, m), 3.77-3.86 (1 H, m), 4.05-4.13 (1 H, m), 6.58 (1 H,d, J = 8.51 Hz), 7.62 (1 H, dd, J = 8.83, 2.52 Hz), 8.14-8.20 (1 H, m).LC-MS 373.2 [M + H]⁺, RT 0.47 min. 3365-ethyl-4-hydroxy-2-oxo-6-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.04 (3 H, t, J = 7.41Hz), 1.94-1.99 (4 H, m), 2.38 (2 H, d, J = 7.57 Hz), 3.44 (4 H, t, J =6.46 Hz), 6.54 (1 H, d, J = 8.51 Hz), 7.58 (1 H, dd, J = 8.83, 2.52 Hz),8.16 (1 H, dd, J = 2.52, 0.63 Hz). LC-MS 330.2 [M + H]⁺, RT 0.55 min.3376-(6-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm1.95-2.06 (m, 1 H), 2.33-2.42 (m, 1 H), 2.46 (s, 6 H), 2.49 (s, 3 H),3.07-3.21 (m, 1 H), 3.33-3.41 (m, 1 H), 3.45-3.56 (m, 1 H), 3.69-3.80(m, 1 H), 3.82-3.93 (m, 1 H), 6.63 (d, J = 8.8 Hz, 1 H), 7.59 (dd, J =8.8, 2.5 Hz, 1 H), 8.09 (d, J = 2.5 Hz, 1 H). LC-MS 359.2 [M + H]⁺, RT0.43 min.

EXAMPLE 355-ethyl-4-hydroxy-6-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 338) Step 1: methyl6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-4-(methoxymethoxy)-2-oxo-1,2-dihydropyridine-3-carboxylate

Methyl6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate,prepared according to Example 2 (1.70 g, 3.7 mmol), was dissolved in DMF(7 mL) and cooled to 0° C. A solution of sodium hydride (60% dispersionin mineral oil, 178 mg, 4.5 mmol) was added to the mixture. After 10 minof vigorous stirring at 0° C., a solution of chloro(methoxy)methane(0.36 g, 4.5 mmol) in DMF (7 mL) was added dropwise to the mixture. Themixture was stirred for an additional 10 min at 0° C., then was warmedto room temperature. After LC/MS showed complete consumption of thestarting material, the reaction was quenched by the addition of anaqueous saturated NaHCO₃ solution (10 mL). The product was extractedwith EtOAc and the combined organics were dried and concentrated. Theresidue was chromatographed on silica gel (0-50% EtOAc in hexanes) toafford the product as a yellow solid (1.6 g, 88% yield).

¹H NMR (500 MHz, Acetone-d) δ ppm 0.91 (t, J=7 Hz, 3H), 2.12 (q, J=7 Hz,2H), 3.54 (s, 3H), 3.55 (s, 3H), 3.78 (s, 3H), 3.85 (s, 3H), 4.86 (s,2H), 5.25 (s, 2H), 6.37 (d, J=3 Hz, 1H), 6.46 (dd, J=8, 2 Hz, 1H), 6.78(d, J=8 Hz, 1H), 7.12 (d, J=8 Hz, 2H), 7.43 (d, J=8 Hz, 2H). LC-MS502.2/504.2 [M+H]⁺, RT 1.42 min.

Step 2: methyl6-(4-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-4-(methoxymethoxy)-2-oxo-1,2-dihydropyridine-3-carboxylate

The intermediate from Step 1 (0.26 g, 0.5 mmol) was mixed withtert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(0.31 g, 1.0 mmol), Pd(OAc)₂ (0.0056 g, 5 mol %), S-Phos (0.0205 g, 10mol %) and K₃PO₄ (0.32 g, 1.5 mmol) in a mixture of toluene/water (1mL/0.1 mL). The mixture was degassed by purging the reaction flask undervacuum and then backfilling with Argon (3×). The reaction mixture washeated at 100° C. with vigorous magnetic stirring for 2 hr until LC/MSshowed complete consumption of starting material. After cooling to roomtemperature, the mixture was filtered and the solids were washed withEtOAc. The filtrate was concentrated and purified by chromatography onsilica gel (0-100% EtOAc in hexanes) to afford the product as a yellowsolid (0.26 g, 80% yield). LC-MS 649.4 [M+H]⁺, RT 1.52 min.

Step 3: methyl6-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

The intermediate from Step 2 (0.26 mg, 0.40 mmol) was mixed with Pd/C(10%, 26 mg) in a mixture of ethyl acetate/methanol (1/1, 5 mL) andstirred under H₂ (1 atm) overnight. The mixture was filtered throughCelite, then concentrated and purified by column chromatography, elutingwith 0-100% EtOAc in hexanes, to afford the product as a colorless oil(0.24 g, 92% yield). LC-MS 651.5 [M+H]⁺, RT 1.59 min.

Step 4

To a solution of the compound prepared from Step 3 (0.13 mg, 0.20 mmol)in dichloromethane (1 mL) was added trifluoroacetic acid (1 mL). Themixture was stirred at room temperature until LC/MS showed completeconsumption of the starting material. The solvent was removed and theresidue was triturated with aqueous NaHCO₃. The solid was collected byfiltration, then washed with H₂O and Et₂O and dried to afford the titlecompound (0.06 g, 84%) as a white solid. LC-MS 355.3 [M−H]⁻, RT 0.86min.

Step 5: methyl5-ethyl-4-hydroxy-6-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

To a solution of the compound prepared from Step 4 (60 mg, 0.17 mmol) indichloromethane/methanol (10/1, 1 mL) was added formaldehyde (0.05 mL,37%, 0.8 mmol) and sodium triacetoxyborohydride (107 mg, 0.51 mmol). Themixture was stirred at room temperature for 1 hr and the reaction wasquenched by the addition of water (a few drops). The solvents wereremoved and the dried residue was used in the next step without furtherpurification. LC-MS 371.2 [M+H]⁺, RT 0.96 min.

Step 6:5-ethyl-4-hydroxy-6-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid

To a solution of the crude material from Step 5 in EtOAc (2 mL) wasadded lithium iodide (100 mg, 0.75 mmol). The reaction mixture washeated to 65° C. and stirred for 1 hr. After cooling, the mixture wasfiltered and the solids were washed with EtOAc. The solids were stirredin 1N HCl (1 mL) for 10 minutes and then filtered. The residue waswashed with water and diethyl ether to provide the title compound as anoff-white solid (25 mg, 42%) over two steps.

¹H NMR (500 MHz, DMSO-d₆) δ 1.01 (t, J=7 Hz, 3H), 1.86-1.91 (m, 2H),2.07-2.10 (m, 2H), 2.28 (q, J=7 Hz, 2H), 2.80 (s, 3H), 2.89-2.91 (m,1H), 3.08-3.11 (m, 2H), 3.52-3.56 (m, 2H), 7.43 (d, J=8 Hz, 2H), 7.48(d, J=8 Hz, 2H), 8.89 (bs, 1H), 12.75 (bs, 1H), 13.93 (bs, 1H). LC-MS357.2 [M+H]⁺, RT 0.51 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and includes compoundsselected from:

Cpd Name 3395-ethyl-6-(4-(1-ethylpiperidin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ 1.01 (t, J= 7 Hz, 3H), 1.27 (t, J = 5 Hz, 3H), 1.83-1.90 (m, 2H), 2.09-2.12 (m,2H), 2.29 (q, J = 7 Hz, 2H), 2.82-2.95 (m, 1H), 3.03-3.08 (m, 2H), 3.17(q, J = 7 Hz, 2H), 3.59-3.63 (m, 2H), 7.43 (d, J = 8 Hz, 2H), 7.48 (d, J= 8 Hz, 2H), 8.89 (bs, 1H), 12.81 (bs, 1H), 13.94 (bs, 1H). LC-MS 371.2[M + H]⁺, RT 0.99*.

EXAMPLE 365-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylicacid (Cpd 340) Step 1: methyl5-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylate

To a solution of the compound prepared from Scheme 1, Step 2 (0.26 mg,0.4 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (1mL). The mixture was stirred at room temperature until LC/MS showedcomplete consumption of the starting material. The solvent was removedunder reduced pressure and the crude product was used in the next stepwithout further purification. LC-MS 353.3 [M−H]⁻, RT 0.96 min.

Step 2:5-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylicacid

To a solution of the crude material from Step 1 in EtOAc (5 mL) wasadded lithium iodide (266 mg, 2.0 mmol). The reaction mixture was heatedto 65° C. and stirred for 1 hr. After cooling, the mixture was filteredand the solids were washed with EtOAc. The solids were stirred in 1N HCl(1 mL) for 10 min and then filtered. The residue was washed with waterand diethyl ether to provide the title compound as an off-white solid(50 mg, 30%) over two steps.

¹H NMR (500 MHz, DMSO-d₆) δ 1.00 (t, J=7 Hz 3H), 2.30 (q, J=7 Hz 2H),2.70-2.75 (m, 2H), 3.34-3.37 (m, 2H), 3.80-3.85 (m, 2H), 6.37 (bs, 1H),7.52 (d, J=13 Hz, 2H), 7.66 (d, J=13 Hz, 2H), 8.79 (bs, 1H), 12.81 (bs,1H), 13.94 (bs, 1H). LC-MS 343.2 [M+H]⁺, RT 0.97 min.

EXAMPLE 375-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 341) Step 1: methyl5-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

Following the procedure in Example 35, Step 5, to methyl5-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylate(60 mg, 0.17 mmol) was added acetaldehyde (0.05 mL, 0.8 mmol) and sodiumtriacetoxyborohydride (107 mg, 0.51 mmol) in a mixture ofdichloromethane/methanol (10/1, 1 mL) to give the title compound whichwas used without further purification in the following step. LC-MS 383.5[M+H]⁺, RT 0.88 min.

Step 2:-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid

Following the procedure in Example 35, Step 6, methyl5-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(crude) and lithium iodide (266 mg, 2.0 mmol) in EtOAc (2 mL) werereacted to give the title compound (23 mg, 40%) over two steps.

¹H NMR (500 MHz, MeOD-d₆) δ 1.08 (t, J=7 Hz, 3H), 1.40 (t, J=8 Hz, 3H),2.43 (q, J=7 Hz, 2H), 2.90-2.95 (m, 2H), 3.19-3.21 (m, 2H), 3.41-3.47(m, 2H), 3.80-3.84 (m, 2H), 6.37 (bs, 1H), 7.48 (d, J=8 Hz, 2H), 7.66(d, J=8 Hz, 2H). LC-MS 369.2 [M+H]⁺, RT 0.98 min.

Using the procedure described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and includes compoundsselected from:

Cpd Name 3425-ethyl-4-hydroxy-6-(4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz,MeOD-d₆) δ 1.11 (t, J = 7 Hz, 3H), 2.43 (q, J = 7 Hz, 2H), 2.97-23.03(m, 2H), 3.05 (s, 3H), 3.59-3.62 (m, 2H), 3.97-4.00 (m, 2H), 6.33 (bs,1H), 7.53 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H). LC-MS 355.2 [M +H]⁺, RT 0.98 min.

EXAMPLE 386-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 343) Step 1. (E)-methyl1-(2,4-dimethoxybenzyl)-6-(4-(2-ethoxyvinyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

Methyl6-(4-chlorophenyl)-1-(2,4-dimethoxybenzyl)-5-ethyl-4-(methoxymethoxy)-2-oxo-1,2-dihydropyridine-3-carboxylatefrom Example 35, Step 1 (0.26 g, 0.5 mmol) was mixed with(E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.2 g,1.0 mmol), Pd(OAc)₂ (0.0067 g, 6 mol %), S-Phos (0.031 g, 15 mol %) andKOH (0.11 g, 1.0 mmol) in acetonitrile (5 mL). The mixture was degassedby purging the reaction flask under vacuum, then backfilling with Argon(3×). The reaction mixture was heated at 80° C. with vigorous magneticstirring overnight. After cooling to room temperature, the mixture wasfiltered and the solids were washed with EtOAc. The filtrate wasconcentrated and purified by chromatography on silica gel (0-100% EtOAcin hexanes) to afford the product as a yellow solid (0.21 g, 77%).

¹H NMR (500 MHz, Acetone-d) δ ppm 0.91 (t, J=7 Hz, 3H), 1.31 (t, J=7 Hz,3H), 2.14 (q, J=7 Hz, 2H), 3.56 (s, 3H), 3.77 (s, 3H), 3.92 (s, 3H),3.96 (q, J=7 Hz, 2H), 4.86 (s, 2H), 5.91 (d, J=13 Hz, 1H), 6.38 (d, J=3Hz, 1H), 6.46 (dd, J=8, 3 Hz, 1H), 6.75 (d, J=8 Hz, 1H), 6.97 (d, J=8Hz, 2H), 7.27-7.31 (m, 3H). LC-MS 494.3 [M+H]⁺, RT 1.62 min.

Step 2. methyl1-(2,4-dimethoxybenzyl)-6-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate

The intermediate from Step 1 (0.1 g, 0.2 mmol) was mixed withHCl/dioxane (4M, 3 mL) and stirred at room temperature for 1 hr. Themixture was diluted with cold water and extracted with ethyl acetate.The organics were washed with water, then dried and concentrated to givethe crude aldehyde which was used in the next step without furtherpurification. The crude material was mixed with dimethylamine (2.0 M inTHF, 0.1 mL, 0.2 mmol) and NaBH(OAc)₃ (0.085 g, 0.4 mmol) indichloromethane (1 mL). The mixture was stirred overnight, and thenwater (a few drops) was added. The solvents were removed under reducedpressure and the residue was purified by chromatography on silica gel(eluting with 10% methanol in CH₂Cl₂) to provide the desired product asa yellow oil (0.03 g, 30% yield).

LC-MS 495.3 [M+H]⁺, RT 1.62 min.

Step 3.6-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid

To a suspension of methyl1-(2,4-dimethoxybenzyl)-6-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylate(0.03 g, 0.06 mmol) in CH₂Cl₂ (1.0 mL) was added TFA (1.0 mL) at roomtemperature. The mixture was stirred at temperature for 2 h andmonitored for completion by LC-MS. The solvent was then removed underreduced pressure and the crude product was used directly in the nextstep without further purification.

To a solution of the crude material in EtOAc (1 mL) was added lithiumiodide (50 mg, 0.38 mmol). The reaction mixture was heated to 65° C. andstirred for 1 hr. After cooling, the mixture was filtered and the solidswere washed with EtOAc. The solids were stirred in 1N HCl (1 mL) for 10min and then filtered. The residue was washed with water and diethylether to provide the title compound as an off-white solid (5 mg, 22%)over two steps.

¹H NMR (500 MHz, MeOD-d₆) δ 1.08 (t, J=7 Hz, 3H), 2.42 (q, J=7 Hz, 2H),3.02 (s, 6H), 3.16-3.20 (m, 2H), 3.46-3.49 (m, 2H), 7.50 (d, J=6 Hz,2H), 7.55 (d, J=6 Hz, 2H). LC-MS 331.2 [M+H]⁺, RT 0.49 min.

EXAMPLE 395-ethyl-6-(1-methyl-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid (Cpd 348) Step 1: methyl 6-chloro-5-ethyl-2-methoxynicotinate

To a solution of 3,5-dichloro-6-ethyl-2H-1,4-oxazin-2-one (10.0 g, 52.0mmol) in DCM (10 mL) was added dry MeOH (10.4 mL, 257 mmol). Thereaction was stirred overnight at room temperature. The mixture waspurified by column chromatography, eluting with EtOAc/hexanes (gradient0-10%) to afford 5-chloro-6-ethyl-3-methoxy-2H-1,4-oxazin-2-one (4.54 g,55%) as an oil.

The product 5-chloro-6-ethyl-3-methoxy-2H-1,4-oxazin-2-one (4.54 g,28.10 mmol) obtained above was mixed with methyl propiolate (6.0 mL,71.80 mmol) and BF₃-etherate (0.26 mL, 2.81 mmol). The mixture washeated at 40° C. for 72 h, then cooled to room temperature and purifiedvia silica gel column eluting with EtOAc/hexanes (gradient 0-15%) toafford methyl 6-chloro-5-ethyl-2-methoxynicotinate (4.84 g, 75%) as anoff-white solid.

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.24 (t, J=7.6 Hz, 3H) 2.70 (q, J=7.6Hz, 2H) 3.91 (s, 3H) 4.04 (s, 3H) 8.05 (s, 1H).

Step 2

6-chloro-5-ethyl-2-methoxynicotinate (0.575 g, 2.50 mmol),bis(pinacolato)diborate (0.762 g, 300 mmol), Pd(dppf)Cl₂ (91.0 mg, 0.1mmol, 4 mol %), and KOAc (0.740 g, 7.50 mmol) were mixed together in aheat-gun dried vial. The vial was placed under vacuum, then back filledwith Argon and dioxane (10 mL) was added. The mixture was heated at 100°C. for 12 hrs and cooled to room temperature, then5-bromo-1-methyl-1H-pyrrole-2-carbaldehyde (0.800 g, 4.3 mmol), freshPd(dppf)Cl₂ (73.0 mg, 0.1 mmol, 4 mol %), K₂CO₃ (1.00 g, 7.60 mmol) andH₂O (2.50 mL) were added. The reaction vial was resealed under Argon andheated at 100° C. for 2 h. The mixture was cooled to room temperature,diluted with H₂O (15 mL) and extracted with DCM (3×20 mL). The combinedorganic phases were washed with NaCl (aqueous saturated, 15 mL), driedover Na₂SO₄, then filtered and concentrated. The residue was purified bycolumn chromatography (EtOAc/hexanes, 0-15% gradient) to afford theproduct methyl5-ethyl-6-(5-formyl-1-methyl-1H-pyrrol-2-yl)-2-methoxynicotinate (0.51g, 68%).

¹H NMR (500 MHz, CHCl₃-d) δ ppm 1.19 (t, J=7.57 Hz, 3H) 2.68 (q, J=7.57Hz, 2H) 3.96 (s, 3H) 3.97 (s, 3H) 4.02-4.06 (m, 3H) 6.41 (d, J=4.10 Hz,1H) 7.02 (d, J=4.10 Hz, 1H) 8.17 (s, 1H) 9.67 (s, 1H).

Step 3

To a solution of methyl5-ethyl-6-(5-formyl-1-methyl-1H-pyrrol-2-yl)-2-methoxynicotinate (0.12g, 0.4 mmol) in DCE (4 mL) was added AcOH (50 μL) and pyrrolidine (100μL, 1.2 mmol). The mixture was stirred at room temperature for 30 min,then NaBH(OAc)₃ (0.17 g, 0.8 mmol) was added. The reaction mixture wasstirred at room temperature for one additional hour, then diluted withDCM and washed with water. The organic phase was dried over Na₂SO₄, thenfiltered and concentrated. The residue was dissolved in 4M HCl (2 mL)and the resulting solution was heated to 80° C. for 1 hr. The mixturewas cooled to room temperature and a precipitate was collected byfiltration to afford the title compound (34 mg, 25% over 2 steps).

¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.24 (t, J=7.53 Hz, 3H) 2.05-2.15 (m,2H) 2.18-2.28 (m, 2H) 2.73 (q, J=7.57 Hz, 2H) 3.23-3.31 (m, 2H)3.59-3.68 (m, 2H) 3.88 (s, 3H) 4.55 (s, 2H) 6.81 (d, J=1.97 Hz, 1H) 7.40(d, J=1.97 Hz, 1H) 8.42 (s, 1H). LC-MS 330.2 [M+H]⁺, RT 0.62 min.

Using the procedures described above, additional compounds describedherein may be prepared by substituting the appropriate startingmaterials, reagents and reaction conditions and includes compoundsselected from:

Cpd Name 3495-ethyl-6-(1-methyl-5-(piperidin-1-ylmethyl)-1H-pyrrol-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.25(s, 3 H) 1.95-2.05 (m, 2 H) 2.70-2.77 (m, 2 H) 3.01-3.11 (m, 4 H)3.57-3.64 (m, 4 H) 3.87 (s, 3 H) 4.41-4.46 (m, 2 H) 6.79-6.84 (m, 1 H)7.40-7.45 (m, 1 H) 8.40-8.45 (m, 1 H). LC-MS 344.2 [M + H]⁺, RT 0.64min. 3505-ethyl-6-(1-methyl-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, DMSO-d₆) δ ppm 1.02(t, J = 7.49 Hz, 3 H) 1.84-2.09 (m, 4 H) 2.35-2.46 (m, 2 H) 3.03-3.15(m, 2 H) 3.41-3.48 (m, 2 H) 3.55 (s, 3 H) 4.42-4.51 (m, 2 H) 6.41 (s, 1H) 6.51 (d, J = 3.78 Hz, 1 H) 8.41 (s, 1 H). LC-MS 328.3 [M − H]⁻, RT0.64 min. 3516-(5-((dimethylamino)methyl)-1-methyl-1H-pyrrol-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.12(t, J = 7.57 Hz, 3 H) 2.46 (q, J = 7.57 Hz, 2 H) 2.95 (s, 6 H) 3.60 (s,3 H) 4.51 (s, 2 H) 6.50 (d, J = 3.86 Hz, 1 H) 6.61 (d, J = 3.86 Hz, 1 H)8.53 (s, 1 H). LC-MS 302.3 [M − H]⁻, RT 0.60 min. 3525-ethyl-6-(1-methyl-5-(piperidin-1-ylmethyl)-1H-pyrrol-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid ¹H NMR (500 MHz, MeOH-d₄) δ ppm 1.13(t, J = 7.61 Hz, 3 H) 1.50-1.62 (m, 1 H) 1.72-1.95 (m, 3 H) 1.97-2.07(m, 2 H) 2.42-2.53 (m, 2 H) 3.00-3.11 (m, 2 H) 3.59 (s, 5 H) 4.47 (s, 2H) 6.51 (d, J = 3.78 Hz, 1 H) 6.60 (d, J = 3.78 Hz, 1 H) 8.53 (s, 1 H).LC-MS 342.3 [M − H]⁻, RT 0.69 min. 3536-(5-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-1-methyl-1H-pyrrol-2-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid LC-MS: 373.4 [M + H]⁺, RT 0.56min.

BIOLOGICAL EXAMPLES

The following biological examples demonstrate the usefulness of thecompounds described herein for treating bacterial infections.

Example 1

The antibacterial activity from a microbroth dilution method may bepresented as the minimum inhibitory concentration (MIC in mg/mL). TheMIC value is the lowest concentration of a drug which preventsmacroscopically visible bacterial growth under test conditions.

In the following tables, an MIC value between >12.5 μg/mL and ≦150 μg/mLis indicated by a single star (*), an MIC value between >3.5 μg/mL and≦12.5 μg/mL is indicated by two stars (**), an MIC value between >1.0μg/mL and ≦3.5 μg/mL is indicated by three stars (***) and an MIC valueof ≦1.0 μg/mL is indicated by four stars (****). The term ND indicatesthat the MIC value was Not Determined.

Antibacterial activity of test compounds against the super sensitiveGram-negative Escherichia coli (E. coli) BAS849 bacterium, the controlGram-negative E. coli 25922 strain and the Gram-positive Staphylococcusaureus (S. aureus) 29213 bacterium are shown in Table 1.

TABLE 1 Cpd BAS849 25922 29213 1 * ND * 2 * * ** 3 **** ** * 4 **** * *5 **** * * 6 ** * * 7 ** * *** 8 **** ** * 9 **** * *** 10 * * *11 * * * 12 **** ** * 13 *** * ** 14 * * * 15 * * * 16 **** ** * 17 ****** * 18 **** ** ** 19 * * * 20 * * * 21 ** * ** 22 * * * 23 * * * 24**** ** * 25 **** ** * 26 * * * 27 **** * * 28 **** * ** 29 *** * *** 30*** * * 31 * * * 32 ** * ** 33 * * * 34 * * * 35 * * * 36 ** * *37 * * * 38 **** *** ** 39 ** * *** 40 * * * 41 * * * 42 **** * *** 43**** * * 44 *** * *** 45 ** * ** 46 * * * 47 *** * ** 48 ** * ** 49 ** *** 50 * * * 51 ** * ** 52 * * * 53 **** *** * 54 * * * 55 **** * ** 56** * ** 57 * * * 58 ** * ** 59 * * * 60 ** * ** 61 ** * ** 62 * * * 63*** * ** 64 ** * * 65 ** * * 66 ** * * 67 ** * *** 68 * * * 69 ** * **70 **** * * 71 *** * ** 72 ** * * 73 ** * ** 74 ** * * 75 *** * *76 * * * 77 *** * ** 78 ** * * 79 **** * ** 80 ** * * 81 *** * ** 82** * *** 83 **** ** ** 84 ** * * 85 **** * ** 86 *** * * 87 **** * * 88**** **** ** 89 * * * 90 **** *** ** 91 * * * 92 * * * 93 **** * * 94**** * * 95 **** ** * 96 **** ** ** 97 **** ** * 98 **** * ** 99 ******** *** 100 **** ** *** 101 **** * * 102 *** * * 103 ** * * 105 ***** * 106 * * * 107 *** * * 108 **** * * 109 **** * ** 110 **** ** * 111**** *** * 112 **** * * 113 ** ** * 114 *** * * 115 **** ** * 116 * * *117 * * * 118 ** * * 119 *** * * 120 **** * * 121 **** ** * 122 ****** * 123 **** **** ** 124 **** **** *** 125 **** ** * 126 **** **** ***127 * * * 128 **** * *** 129 **** *** ** 130 **** *** ** 131 **** ** *132 **** *** ** 133 *** * * 134 **** ** * 135 **** * * 136 *** * * 137**** * * 138 * * * 139 **** ** ** 140 **** ** * 141 **** * ** 142*** * * 143 ** * * 144 **** *** ** 145 **** * *** 146 **** * * 147 ****** ** 148 ** * * 149 **** *** * 150 **** *** * 151 **** *** * 152 ******* ** 153 **** **** *** 154 **** *** ** 155 **** *** ** 156 **** * *157 **** ** * 158 **** ** ** 159 *** * * 160 **** *** * 161 **** *** *162 ** * * 163 **** ** * 164 **** *** ** 165 *** * * 166 **** ** * 167*** * * 168 **** * * 169 **** *** * 170 * * * 171 ** * * 172 **** ** *173 **** *** * 174 **** **** * 175 **** *** * 176 * * * 177 **** **** *178 **** **** * 179 *** ** * 180 *** * * 181 ** * * 182 **** **** * 183**** ** * 184 *** * * 185 **** ** * 186 * * * 187 **** ** * 188 ****** * 189 **** ** * 190 *** * * 191 **** *** * 192 **** ** ** 193 *** * *194 *** * ** 195 *** ** * 196 * * * 197 ** * * 198 **** ** * 199 **** **** 200 *** ** * 201 ** * * 202 *** * * 203 *** * * 204 *** * * 205*** * * 206 *** ** * 207 ** * * 208 *** ** * 209 ** * * 210 *** * * 211**** ** * 212 **** ** * 213 *** * * 214 *** * * 215 *** ** * 216 * * *217 **** ** ** 218 *** ** * 219 **** * * 220 ** * * 221 *** ** * 222*** * * 223 * * * 224 **** * * 225 **** ** * 226 **** *** ** 227 ******* *** 228 * * * 230 **** *** ** 231 **** *** * 232 **** *** ** 233**** ** * 234 **** *** * 235 *** * * 236 **** *** ** 237 **** **** **238 **** *** * 239 **** **** * 240 **** *** * 241 **** **** * 242 ******* * 243 **** *** * 244 **** * *** 245 **** ** ** 246 **** *** * 247**** ** ** 248 *** * * 249 * * * 250 ** * * 251 * * * 252 **** *** * 253**** * ** 254 **** *** * 255 ** * ** 256 **** *** ** 257 **** **** * 258**** *** ** 259 **** *** * 260 ** ** *** 261 **** ** ** 262 **** *** **263 **** *** * 264 **** *** ** 265 *** ** * 266 *** * ** 267 *** ** *268 *** ** ** 269 **** **** ** 270 **** **** ** 271 **** ** * 272 ******** ** 273 **** *** * 274 *** * * 275 **** **** * 276 **** * *** 277**** *** ** 278 **** ** ** 279 **** *** * 280 **** * * 281 ** * * 282**** * * 283 ** * * 284 ** * * 285 **** **** ** 286 **** *** *** 287**** *** ** 288 **** *** *** 289 **** *** *** 290 **** *** * 291 ***** * 292 **** *** * 293 **** ** ** 294 **** * *** 295 *** * * 296 ******* *** 297 **** * ** 298 ** * * 299 *** * * 300 *** * *** 301 **** ******** 302 **** *** **** 303 **** * * 304 **** ** ** 305 **** * * 306 ****** ** 307 **** * ** 308 *** * * 309 **** * ** 310 * * * 311 ** * * 312**** * * 313 **** * * 314 ** * * 315 *** * * 316 * * * 317 ** ** * 318** * * 319 **** ** * 320 ** * * 321 *** * * 322 **** **** ** 323 ***** * 324 ** * * 325 **** ** * 326 **** ** * 327 ** * * 328 **** ** *329 * * * 330 *** * * 331 *** * * 332 * * * 333 *** * * 334 ** * * 335** * * 336 *** * * 337 * * * 338 * * * 339 ** * * 340 ** * * 341 *** * *342 *** ** * 343 ** * * 343 ** * * 344 * * * 345 * * * 346 * * * 347 ***** * 348 ** * * 349 * * * 350 * * * 351 * * * 352 * * * 353 * * *

Example 2

Antibacterial activity of test compounds against the quinolone resistantE. coli LZ3111 bacterium is shown in Table 2. The E. coli LZ3111 strainis genetically engineered and possesses double mutations in both thegyrase A and par C regions of the topoisomerase subunits. Mutations inthese regions are known to confer a high level resistance to thequinolone class of antibiotics.

TABLE 2 Cpd LZ3111 3 * 4 * 5 *** 8 * 12 * 16 * 17 * 18 * 20 ** 24 * 25 *30 * 38 * 41 * 42 * 44 * 45 * 49 * 50 * 55 * 68 * 75 * 83 * 84 * 85 *86 * 87 *** 88 * 90 * 92 * 93 * 94 * 95 * 96 * 97 * 99 * 100 * 101 *105 * 107 * 108 * 110 * 111 * 112 * 113 * 115 * 116 * 117 * 121 * 123 *124 * 126 * 128 * 129 * 130 * 131 * 132 * 134 * 135 * 136 * 139 * 140 *141 * 144 * 147 * 149 * 150 * 151 * 152 * 153 * 154 * 155 * 157 * 158 *159 * 160 * 161 * 163 * 164 * 165 * 166 * 167 * 168 * 169 * 173 * 174 *175 * 177 * 178 * 179 * 182 * 183 * 184 * 185 * 187 * 188 * 190 * 191 *192 * 193 * 194 * 195 * 196 * 197 * 198 * 199 * 200 * 201 * 202 * 203 *204 * 205 * 206 * 207 * 208 * 209 * 210 * 211 * 212 * 213 * 214 * 215 *216 * 218 * 219 * 220 * 221 * 222 * 223 * 224 * 225 * 226 * 227 * 228 *230 * 231 * 232 * 233 * 234 * 235 * 236 * 237 * 238 * 239 * 240 * 241 *242 * 243 * 244 * 245 * 247 * 248 * 249 * 250 * 251 * 252 ** 253 * 254** 255 * 256 *** 257 ** 258 **** 259 *** 260 **** 261 *** 262 **** 263** 264 *** 265 ** 266 ** 267 ** 268 *** 269 ** 270 *** 271 ** 272 ****273 * 274 * 275 *** 276 * 277 ** 278 * 279 **** 280 * 281 * 282 * 283 *284 * 285 ** 286 * 287 * 288 ** 289 * 290 ** 291 * 292 * 293 * 294 *295 * 296 **** 297 * 300 * 301 * 302 * 304 * 306 * 310 * 312 * 313 * 314** 315 * 316 * 317 * 318 * 319 * 320 * 321 * 322 * 323 ** 324 * 325 *326 * 327 * 328 ** 329 ** 330 * 331 ** 332 * 333 * 334 * 335 **** 336 **337 **** 338 * 339 * 340 * 341 ** 342 ** 343 * 348 * 349 * 350 * 351 *352 * 353 *

Example 3

Antibacterial activity of test compounds against MDR E. coli strains isshown in Table 3. The E. coli ELZ4000 and E. coli ELZ4251 strains areMDR clinical isolates.

TABLE 3 Cpd ELZ4251 ELZ4000 3 * * 4 * * 5 *** ** 8 * * 12 * * 16 * *17 * * 18 * * 24 * * 25 * * 38 * * 75 * * 83 * * 84 * * 85 * * 87 ****** 88 * * 90 * * 92 * * 93 * * 94 * * 95 * * 96 * * 97 * * 99 * *100 * * 101 * * 105 * * 107 * * 108 * * 110 * * 111 * * 115 * * 121 * *123 * * 124 * * 126 * * 128 * * 129 * * 130 * * 131 * * 132 * * 134 * *139 * * 140 * * 141 * * 144 * * 147 * * 149 * * 150 * * 151 * * 152 * *153 * * 154 * * 155 * * 157 * * 158 * * 160 * * 161 * * 163 * * 164 * *174 * * 177 * * 178 * * 179 * * 182 * * 183 * * 185 * * 187 * * 202 * *203 * * 206 * * 208 * * 216 * * 244 * * 246 ** * 252 * * 254 ** * 256** * 257 *** ** 258 ** * 259 ** ** 260 *** ** 261 ** * 262 *** ***263 * * 264 ** * 265 ** * 266 * * 268 ** * 269 * * 270 ** * 271 ** * 272*** ** 273 * * 275 *** ** 277 * * 279 *** ** 285 ** * 290 ** * 296 ** *300 * * 301 * * 302 * * 304 * * 306 * * 310 * *

Example 4

Antibacterial activity of test compounds against the Gram-negativeAcinetobacter baumannii (A. baumannii) BAA747 and Klebsiella pneumoniae(K. pneumoniae) 35657 bacterium and the resistant A. baumannii MXX2240and K. pneumoniae MXX1232 strains are shown in Table 4. The MMX strainsare MDR clinical isolates.

TABLE 4 Cpd BAA747 MMX2240 35657 MMX1232 4 ND ND ** ND 5 ** **** * *20 * ** * * 25 ** *** ND * 75 * ND ND ND 84 * ND ND ND 86 * * * * 87 ****** * * 88 **** * **** * 90 *** ** ** * 92 * ND ND ND 93 * ND * ND 94 *ND * ND 95 ND ND * ND 97 ND ND ** ND 99 ND ND ** ND 100 ND ND * ND 101ND ND ** ND 124 **** * ND * 126 **** * ND * 173 ** * *** * 177 *** ***** * 178 *** * **** * 192 * ND * ND 217 * ND ** ND 219 * ND * ND 225 *ND *** ND 226 *** * ** * 227 *** * ** * 231 * ND *** ND 232 *** * *** *246 * * *** * 247 * ND ** ND 254 ** * ** * 256 * * *** * 257 *** * *** *258 * ** *** * 259 ** * *** * 260 * ND ** ND 261 * * * * 262 ** ****** * 263 ** * ** * 264 * * ** * 265 * * ** * 266 * ND * ND 267 * ND **ND 268 * * * * 269 **** ** **** * 270 **** * **** * 271 * ND ND ND 272*** ** **** * 275 *** *** *** * 276 * ND * ND 277 ** * *** * 279 * **** * 285 **** * *** * 286 ** * * * 288 *** *** ** * 292 ** ND *** ND293 * ND * ND 296 * ** *** * 310 * ND ND ND 312 ** * ** * 313 ** * ** *314 * * * * 315 * * * * 316 * * * * 317 * * ** * 318 * * * * 319 * *** * 320 * * ** * 321 * * ** * 322 *** * *** * 323 * * * * 324 * * * *325 ** * ** * 326 *** ** ** * 327 * * * * 328 * ** ** * 329 * * * *330 * * * * 331 * * * * 332 * * * * 333 * * * * 334 * * * * 335 * * * *336 * * * * 337 * * * * 338 * * * * 339 * * * * 340 * * ** * 341 * *** * 342 * * ** * 343 * * * *

Example 5

Antibacterial activity of test compounds against the Gram-negativebacterium Pseudomonas aeruginosa (P. aeruginosa) 27853 is shown in Table5.

TABLE 5 Cpd 27853 4 * 5 * 8 * 12 * 20 * 75 * 83 * 84 * 85 * 86 * 87 * 88** 90 * 92 * 93 * 94 * 95 * 96 * 97 * 99 ** 100 * 101 * 107 * 108 *110 * 111 * 115 * 123 ** 126 ** 128 * 129 * 131 * 139 * 140 * 141 *144 * 147 * 149 * 150 * 151 * 152 ** 153 ** 154 * 155 * 157 * 158 *173 * 174 * 177 *** 178 * 192 * 202 * 203 * 216 * 217 * 219 * 225 *226 * 227 ** 231 * 232 * 244 * 246 * 247 * 252 * 254 ** 256 * 257 *258 * 259 * 260 * 261 * 262 * 263 * 264 * 265 * 266 * 267 * 268 * 269*** 270 *** 271 * 272 ** 275 ** 276 * 277 * 279 * 285 ** 286 * 288 **290 * 292 ** 293 * 296 * 301 ** 302 ** 304 * 310 * 312 * 313 * 314 *315 * 316 * 317 * 318 * 319 * 320 * 321 * 322 ** 323 * 324 * 325 * 326 *327 * 328 * 329 * 330 * 331 * 332 * 333 * 334 * 335 * 336 * 337 * 338 *339 * 340 * 341 * 342 * 343 *

Example 6

Antibacterial activity of test compounds against the Gram-negativebacteria Haemophilus influenzae (H. influenzae) 49247, Moraxellacatarrhalis (M. catarrhalis) 25238 and Neisseria meningitidis (N.meningitidis) 13090 is shown in Table 6.

TABLE 6 Cpd 49247 25238 13090 1 **** ** ** 2 **** **** **** 3 ND ******** 5 *** *** **** 6 **** ** **** 7 **** **** *** 8 **** **** **** 9**** **** **** 11 **** * * 12 **** **** **** 13 **** **** **** 14**** * * 16 **** **** ND 17 **** **** **** 18 **** **** ND 22 * * ** 38ND **** ND 53 ND **** ND 75 ND * ND 82 **** **** **** 83 **** **** ****84 **** ** *** 86 **** *** **** 87 *** *** **** 88 ** **** **** 89**** * * 90 ND **** **** 91 *** **** ** 92 *** * ** 93 **** **** **** 94**** **** **** 95 **** **** **** 96 **** **** **** 97 **** **** **** 98*** ** **** 99 **** **** **** 100 **** **** **** 101 **** **** **** 102*** **** *** 103 **** * ** 105 ** ** *** 106 **** * ** 107 **** ******** 108 **** **** **** 109 **** **** **** 110 **** **** **** 111 ******** **** 114 **** **** **** 115 **** **** **** 121 **** **** **** 123**** **** **** 124 **** **** **** 126 **** **** **** 128 *** **** ****132 **** **** **** 134 **** ** **** 138 * **** * 140 **** **** **** 141**** **** **** 142 ** *** **** 144 **** **** **** 145 **** **** **** 146*** **** **** 147 **** **** **** 148 * * ** 150 **** **** **** 151 ******** **** 154 **** **** **** 155 **** **** **** 156 **** **** **** 157**** **** **** 160 **** **** ND 177 ND **** **** 182 ND **** **** 185 ND*** **** 187 ND *** **** 246 *** ** *** 254 * * *** 256 ** *** **** 257*** *** **** 258 ** *** **** 259 *** ** **** 260 * ** *** 261 * ** ****262 ** ** *** 263 ** *** *** 264 ** *** **** 265 * ** *** 268 * ** **269 **** **** **** 270 **** **** **** 272 **** **** **** 273 ND *** ***275 **** **** **** 277 *** *** **** 279 ** ** * 285 **** *** **** 296 **** **** 298 ** * ** 300 * **** **** 302 **** **** **** 304 **** ******** 306 **** **** **** 310 ND * ND

Example 7 Combinations with Antibacterial Agents

The in vitro effects of Compound 269 in combination with ciprofloxacinwere investigated in various organisms using the microdilutioncheckerboard method for the measurement of antibiotic synergy. Assayscan be performed in a 96-well checkerboard titration format, with serialdilutions of each compound to identify the lowest MIC value (μg/mL) foreach drug where the bacterial culture is completely inhibited. Theability of compounds to either act synergistically, additively,indifferently or antagonistically can be determined. Synergy is definedsuch that when the elements A and B are combined, the result is greaterthan the expected arithmetic sum A+B.

The calculated fractional inhibitory concentration (FIC) is aquantitative measure of drug interactions: where values ≦0.5=synergy,values between >0.5 and <2=additive, values between ≧2 and≦4=indifference, and values >4=antagonism. Table 7 shows the MIC (μg/mL)for ciprofloxacin (Cipro), Compound 269 (Cpd 269), and the combinationproduct (Cipro: 269). The FIC was calculated using the checkerboardmethod in a 96-well microtiter plate. Combinations that demonstrated nodifference (Indiff) in the resulting activity and those thatdemonstrated synergistic (Syn) or additive (Add) activity are indicated.

TABLE 7 Cpd Cipro 269 Cipro:269 Strain MIC MIC MIC FIC Result E. coli25922 0.013 0.19 0.003:0.049 0.49 Syn E. coli 3111 125 3.1 125:3.1  2Indiff A. baumannii BAA747 0.098 0.39 0.012:0.098 0.28 Syn A. baumannii(MDR) 125 12.5 31.2:3.12 0.5 Syn K. pneumoniae 35657 0.01 0.390.0008:0.098  0.31 Syn P. aeruginosa 27853 0.2 1.6 0.012:0.78  0.56 AddS. aureus 29213 0.39 3.12 0.098:0.78  0.5 Syn S. aureus (MDR) 31.2 6.27.8:3.1 0.75 AddResults:

The results shown in Table 7 suggest that development of a combinationtherapy is an option to treat certain infections.

Combination therapy can be applied with any quinolone antibioticincluding, without limitation, one or more of Ciprofloxacin, Enoxacin,Gatifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid,Norfloxacin or Ofloxacin.

In addition, combination therapy can be applied with any non-quinoloneantibiotic including, without limitation, one or more of Amikacin,Amoxicillin, Ampicillin, Arsphenamine, Azithromycin, Azlocillin,Aztreonam, Bacitracin, Capreomycin, Carbenicillin, Cefaclor, Cefadroxil,Cefalexin, Cefalotin (Cefalothin), Cefamandole, Cefazolin, Cefdinir,Cefditoren, Cefixime, Cefoperazone, Cefotaxime, Cefoxitin, Cefpodoxime,Cefprozil, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone,Cefuroxime, Chloramphenicol, Cilastatin, Clarithromycin, Clavulanate,Clindamycin, Clofazimine, Cloxacillin, Colistin, Cycloserine,Dalfopristin, Dapsone, Daptomycin, Dicloxacillin, Dirithromycin,Doripenem, Doxycycline, Erythromycin, Ethambutol, Ethionamide,Flucloxacillin, Fosfomycin, Furazolidone, Fusidic acid, Gentamicin,Imipenem, Isoniazid, Kanamycin, Lincomycin, Linezolid, Loracarbef,Mafenide, Meropenem, Methicillin, Metronidazole, Mezlocillin,Minocycline, Mupirocin, Nafcillin, Neomycin, Netilmicin, Nitrofurantoin,Oxacillin, Oxytetracycline, Paromomycin, Penicillin G, Penicillin V,Piperacillin, Platensimycin, Polymyxin B, Pyrazinamide, Quinupristin,Rapamycin, Rifabutin, Rifampicin, Rifampin, Rifapentine, Rifaximin,Roxithromycin, Silver sulfadiazine, Spectinomycin, Streptomycin,Sulbactam, Sulfacetamide, Sulfadiazine, Sulfamethizole,Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole,Tazobactam, Teicoplanin, Telavancin, Telithromycin, Temocillin,Tetracycline, Thiamphenicol, Ticarcillin, Tigecycline, Tinidazole,Tobramycin, Trimethoprim, Troleandomycin or Vancomycin.

Without regard to whether a document cited herein was specifically andindividually indicated as being incorporated by reference, all documentsreferred to herein are incorporated by reference into the presentapplication for any and all purposes to the same extent as if eachindividual reference was fully set forth herein.

Although certain embodiments have been described in detail above, thosehaving ordinary skill in the art will clearly understand that manymodifications are possible in the embodiments without departing from theteachings thereof. All such modifications are intended to be encompassedwithin the claims included herein.

What is claimed is:
 1. A compound of Formula (I):

or a form thereof, wherein R₁ is phenyl, optionally substituted withone, two or three substituents each selected from R₅ and one additionalsubstituent selected from R₆; R₂ is halogen, cyano, C₁₋₈alkyl,halo-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl, formyl-C₁₋₈alkyl,C₁₋₈alkoxy-C₁₋₈alkyl, C₂₋₈alkenyl, C₂₋₈alkynl, carboxyl, amino,C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₃₋₁₄cycloalkyl, C₃₋₈cycloalkyl-oxy, aryl or aryl-C₁₋₈alkyl, whereineach instance of aryl is optionally substituted with one halogensubstituent; R₃ is hydroxyl; R₄ is hydrogen; R₅ is halogen, hydroxyl,oxo, cyano, nitro, C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl, halo-C₁₋₈alkyl,C₁₋₈alkoxy, halo-C₁₋₈alkoxy, C₁₋₈alkyl-thio, carboxyl,C₁₋₈alkyl-carbonyl, C₁₋₈alkoxy-carbonyl, amino-carbonyl, amino,C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, C₂₋₈alkenyl-amino,(C₂₋₈alkenyl)₂-amino, C₂₋₈alkynyl-amino, (C₂₋₈alkynyl)₂-amino,amino-C₁₋₈alkyl, C₁₋₁₀alkyl-amino-C₁₋₈alkyl,(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₂₋₈alkenyl-amino-C₁₋₈alkyl,(C₂₋₈alkenyl)₂-amino-C₁₋₈alkyl, C₂₋₈alkynyl-amino-C₁₋₈alkyl,(C₂₋₈alkynyl)₂-amino-C₁₋₈alkyl, halo-C₁₋₈alkyl-amino,(halo-C₁₋₈alkyl)₂-amino, halo-C₁₋₈alkyl-amino-C₁₋₈alkyl,(halo-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl-amino,(C₁₋₈alkoxy-C₁₋₈alkyl,C₁₋₈alkyl)-amino, (C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino,C₁₋₈alkoxy-C₁₋₈alkyl-amino-C₁₋₈alkyl,(C₁₋₈alkoxy-C₁₋₈alkyl,C₁₋₈alkyl)-amino-C₁₋₈alkyl,(C₁₋₈alkoxy-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, amino-C₁₋₈alkyl-amino,(amino-C₁₋₈alkyl,C₁₋₈alkyl)amino, C₁₋₈alkyl-amino-C₁₋₈alkyl-amino,(C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl)amino,(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino,amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,(amino-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,(C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino-C₁₋₈alkyl, hydroxyl-amino,hydroxyl-C₁₋₈alkyl-amino, (hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino,(hydroxyl-C₁₋₈alkyl)₂-amino, hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl-amino,(hydroxyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl)amino,(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl-amino,[(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,C₁₋₈alkyl]amino,(C₁₋₈alkyl-carbonyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, C₁₋₈alkyl-amino-carbonyl,(C₁₋₈alkyl)₂-amino-carbonyl or(C₁₋₈alkyl)₂-amino-carbonyl-C₁₋₈alkyl-amino-C₁₋₈alkyl; R₆ isC₃₋₁₄cycloalkyl, C₃₋₁₄cycloalkyl-C₁₋₈alkyl, C₃₋₁₄cycloalkyl-oxy,C₃₋₁₄cycloalkyl-C₁₋₈alkoxy, C₃₋₁₄cycloalkyl-amino,C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl,(C₃₋₁₄cycloalkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(C₃₋₁₄cycloalkyl)₂-amino-C₁₋₈alkyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(C₃₋₁₄cycloalkyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(C₃₋₁₄cycloalkyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, aryl, aryl-C₁₋₈alkyl,aryl-C₁₋₈alkoxy, aryl-amino, (aryl,C₁₋₈alkyl)amino, (aryl)₂-amino,aryl-amino-C₁₋₈alkyl, (aryl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(aryl)₂-amino-C₁₋₈alkyl, aryl-C₁₋₈alkyl-amino,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heteroaryl, heteroaryl-C₁₋₈alkyl,heteroaryl-amino, heteroaryl-C₁₋₈alkyl-amino,(heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino, (heteroaryl-C₁₋₈alkyl)₂-amino,heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, heterocyclyl,heterocyclyl-C₁₋₈alkyl, heterocyclyl-oxy, heterocyclyl-C₁₋₈ alkoxy,heterocyclyl-amino, (heterocyclyl,C₁₋₈alkyl)amino,(heterocyclyl)₂-amino, heterocyclyl-amino-C₁₋₈alkyl,(heterocyclyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(heterocyclyl)₂-amino-C₁₋₈alkyl,(heterocyclyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl,heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(heterocyclyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(heterocyclyl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heterocyclyl-oxy-amino,(heterocyclyl-oxy,C₁₋₈alkyl)amino, (heterocyclyl-oxy)₂-amino,(heterocyclyl-oxy-C₁₋₈alkyl,C₁₋₈alkyl)amino, heterocyclyl-carbonyl orheterocyclyl-carbonyl-oxy; wherein each instance of heterocyclyl isoptionally substituted with one, two or three substituents each selectedfrom R₇; and, wherein each instance of C₃₋₁₄cycloalkyl, aryl andheteroaryl is optionally substituted with one, two or three substituentseach selected from R₈; R₇ is azido, halogen, hydroxyl, oxo, cyano,nitro, C₁₋₈alkyl, halo-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl,C₁₋₈alkoxy-C₁₋₈alkyl, C₁₋₈ alkoxy, halo-C₁₋₈ alkoxy,hydroxyl-C₁₋₈alkoxy, carboxyl, C₁₋₈alkyl-carbonyl, C₁₋₈alkoxy-carbonyl,amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, halo-C₁₋₈alkyl-amino,(halo-C₁₋₈alkyl)₂-amino, halo-C₁₋₈alkyl-amino-C₁₋₈alkyl,(halo-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino-C₁₋₈alkyl C₁₋₈alkyl-thio,amino-carbonyl, C₁₋₈alkyl-amino-carbonyl, (C₁₋₈alkyl)₂-amino-carbonyl,C₁₋₈alkyl-carbonyl-amino,(carboxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-carbonyl-amino, C₃₋₁₄cycloalkyl,C₃₋₁₄cycloalkyl-amino, aryl, aryl-C₁₋₈alkyl, aryl-amino,(aryl,C₁₋₈alkyl)amino, (aryl)₂-amino, aryl-C₁₋₈alkyl-amino,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, aryl-amino-C₁₋₈alkyl,(aryl,C₁₋₈alkyl)amino-C₁₋₈alkyl, (aryl)₂-amino-C₁₋₈alkyl,aryl-amino-carbonyl, aryl-C₁₋₈ alkoxy, aryl-C₁₋₈ alkoxy-carbonyl-amino,heteroaryl, heteroaryl-C₁₋₈alkyl, heteroaryl-amino, (heteroaryl)₂-amino,heteroaryl-C₁₋₈alkyl-amino, (heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino,(heteroaryl-C₁₋₈alkyl)₂-amino, heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(heteroaryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heterocyclyl,heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl orheterocyclyl-oxy; wherein each instance of C₃₋₁₄cycloalkyl is optionallysubstituted with one substituent selected from R₉; wherein each instanceof aryl is optionally substituted with one substituent selected fromR₁₀; and, wherein each instance of heterocyclyl and heteroaryl isoptionally substituted with one substituent selected from R₁₁; R₈ isazido, halogen, hydroxyl, cyano, nitro, C₁₋₈alkyl, halo-C₁₋₈alkyl,C₁₋₈alkoxy, C₁₋₈alkoxy-C₁₋₈alkyl, halo-C₁₋₈alkoxy, carboxyl,C₁₋₈alkoxy-carbonyl, amino, C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino,C₁₋₈alkyl-thio, aryl, aryl-C₁₋₈alkoxy, heteroaryl, heterocyclyl,heterocyclyl-C₁₋₈alkyl or heterocyclyl-oxy; R₉ is amino,C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl oraryl-C₁₋₈alkyl-amino; R₁₀ is halogen; and, R₁₁ is halogen, hydroxyl,C₁₋₈alkyl, halo-C₁₋₈alkyl, C₁₋₈alkoxy, C₁₋₈alkoxy-C₁₋₈alkyl,halo-C₁₋₈alkoxy, amino, C₁₋₈alkyl-amino or (C₁₋₈alkyl)₂-amino; whereinthe form of the compound is selected from a free acid, free base,hydrate, solvate, clathrate, isotopologue, racemate, enantiomer,diastereomer, stereoisomer, polymorph or tautomer form thereof.
 2. Thecompound of claim 1, wherein R₂ is cyano, C₁₋₈alkyl, halo-C₁₋₈alkyl,hydroxyl-C₁₋₈alkyl, formyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl, C₂₋₈alkenyl,C₂₋₈alkynl, carboxyl, C₃₋₁₄cycloalkyl, aryl or aryl-C₁₋₈alkyl, whereineach instance of aryl is optionally substituted with one halogensubstituent; R₅ is halogen, oxo, cyano, C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl,C₁₋₈alkoxy, carboxyl, amino-carbonyl, amino, C₁₋₈alkyl-amino,(C₁₋₈alkyl)₂-amino, (C₂₋₈alkenyl)₂-amino, amino-C₁₋₈alkyl,C₁₋₁₀alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, C₂₋₈alkenyl-amino-C₁₋₈alkyl, C₂₋₈alkynyl-amino-C₁₋₈alkyl,halo-C₁₋₈alkyl-amino, halo-C₁₋₈alkyl-amino-C₁₋₈alkyl,(hydroxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino,(C₁₋₈alkoxy-C₁₋₈alkyl,C₁₋₈alkyl)-amino-C₁₋₈alkyl,(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino,amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl-amino-C₁₋₈alkyl,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino-C₁₋₈alkyl,(C₁₋₈alkyl-carbonyl,C₁₋₈alkyl)amino-C₁₋₈alkyl or(C₁₋₈alkyl)₂-amino-carbonyl-C₁₋₈alkyl-amino-C₁₋₈alkyl; R₆ isC₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl,(C₃₋₁₄cycloalkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, aryl, aryl-amino,(aryl,C₁₋₈alkyl)amino, aryl-amino-C₁₋₈alkyl,aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, heteroaryl,heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, heterocyclyl,heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl,(heterocyclyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(heterocyclyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl,heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl or(heterocyclyl-oxy-C₁₋₈alkyl,C₁₋₈alkyl)amino; wherein each instance ofheterocyclyl is optionally substituted with one, two or threesubstituents each selected from R₇; and, wherein each instance ofheteroaryl is optionally substituted with one, two or three substituentseach selected from R₈; R₇ is azido, halogen, hydroxyl, oxo, cyano,C₁₋₈alkyl, halo-C₁₋₈alkyl, hydroxyl-C₁₋₈alkyl, C₁₋₈alkoxy-C₁₋₈alkyl,C₁₋₈alkoxy, carboxyl, C₁₋₈alkyl-carbonyl, C₁₋₈alkoxy-carbonyl, amino,C₁₋₈alkyl-amino, (C₁₋₈alkyl)₂-amino, amino-C₁₋₈alkyl,C₁₋₈alkyl-amino-C₁₋₈alkyl, (C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,[(C₁₋₈alkyl)₂-amino-C₁₋₈alkyl,C₁₋₈alkyl]amino-C₁₋₈alkyl(C₁₋₈alkyl)₂-amino-carbonyl, C₁₋₈alkyl-carbonyl-amino,(carboxyl-C₁₋₈alkyl,C₁₋₈alkyl)amino-carbonyl-amino, C₃₋₁₄cycloalkyl,C₃₋₁₄cycloalkyl-amino, aryl, aryl-C₁₋₈alkyl, aryl-amino,(aryl,C₁₋₈alkyl)amino, aryl-C₁₋₈alkyl-amino,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino, (aryl-C₁₋₈alkyl)₂-amino,aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl,(aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, aryl-amino-C₁₋₈alkyl,aryl-C₁₋₈alkoxy, aryl-C₁₋₈alkoxy-carbonyl-amino, heteroaryl,heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, heterocyclyl,heterocyclyl-C₁₋₈alkyl, heterocyclyl-amino-C₁₋₈alkyl orheterocyclyl-oxy; wherein each instance of C₃₋₁₄cycloalkyl is optionallysubstituted with one substituent selected from R₉; wherein each instanceof aryl is optionally substituted with one substituent selected fromR₁₀; and, wherein each instance of heterocyclyl and heteroaryl isoptionally substituted with one substituent selected from R₁₁; R₈ isC₁₋₈alkyl; R₉ is amino, (C₁₋₈alkyl)₂-amino or aryl-C₁₋₈alkyl-amino; R₁₀is halogen; and, R₁₁ is C₁₋₈alkyl.
 3. The compound of claim 1, whereinR₂ is C₁₋₈alkyl selected from the group consisting of methyl, ethyl,propyl and isopropyl; hydroxyl-C₁₋₈alkyl selected from the groupconsisting of hydroxyl-methyl, hydroxyl-ethyl and hydroxyl-propyl;formyl-C₁₋₈alkyl selected from the group consisting of formylmethyl,formylethyl and formylpropyl; C₃₋₁₄cycloalkyl selected from the groupconsisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; arylselected from phenyl; or, aryl-C₁₋₈alkyl selected from benzyl.
 4. Thecompound of claim 1, wherein R₆ is C₃₋₁₄cycloalkyl-amino-C₁₋₈alkyl,wherein C₃₋₁₄cycloalkyl is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;(C₃₋₁₄cycloalkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein C₃₋₁₄cycloalkyl isselected from the group consisting of cyclopropyl, cyclobutyl andcyclopentyl; C₃₋₁₄cycloalkyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, whereinC₃₋₁₄cycloalkyl is selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl; aryl, wherein arylis selected from phenyl; aryl-C₁₋₈alkoxy, wherein aryl is selected fromphenyl; aryl-amino, wherein aryl is selected from phenyl;(aryl,C₁₋₈alkyl)amino, wherein aryl is selected from phenyl;aryl-amino-C₁₋₈alkyl, wherein aryl is selected from phenyl;aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein aryl is selected from phenyl;(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein aryl is selected fromphenyl; (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, wherein aryl is selected fromphenyl; heteroaryl, wherein heteroaryl is selected from the groupconsisting of pyrrolyl, thiazolyl, 1H-1,2,3-triazolyl, 1H-tetrazolyl,2H-tetrazolyl, imidazolyl and pyridinyl;heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heteroaryl is selectedfrom the group consisting of pyridin-2-yl, pyridin-3-yl andpyridin-4-yl; (heteroaryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, whereinheteroaryl is selected from the group consisting of pyridin-3-yl andpyridin-4-yl; heterocyclyl, wherein heterocyclyl is selected from thegroup consisting of azetidinyl, pyrrolidinyl, tetrahydrofuranyl,piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,2,5-dihydro-1H-pyrrolyl, dihydro-1H-imidazolyl,1,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl,tetrahydro-2H-pyranyl, 3,4-dihydroisoquinolin-(1H)-yl,1,2,3,4-tetrahydroisoquinolinyl,hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,(cis)-octahydrocyclopenta[c]pyrrolyl,hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,5H-pyrrolo[3,4-b]pyridin-(7H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,(4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,octahydro-6H-pyrrolo[3,4-b]pyridinyl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,(3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,(3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl,(3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl,2-azabicyclo[2.2.1]hept-5-enyl, 3-azabicyclo[3.1.0]hexanyl,(1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,(cis,cis)-3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.0]hexanyl,(1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,(1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl and2,8-diazaspiro[4.5]decanyl; heterocyclyl-C₁₋₈alkyl, wherein heterocyclylis selected from the group consisting of azetidinyl, pyrrolidinyl,tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl,1,4-diazepanyl, 1,3-dioxolanyl, 2,5-dihydro-1H-pyrrolyl,dihydro-1H-imidazolyl, 1,4,5,6-tetrahydropyrimidinyl,1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl,3,4-dihydroisoquinolin-(1H)-yl, 1,2,3,4-tetrahydroisoquinolinyl,hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,(cis)-octahydrocyclopenta[c]pyrrolyl,hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,5H-pyrrolo[3,4-b]pyridin-(7H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl,hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,(4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl,octahydro-6H-pyrrolo[3,4-b]pyridinyl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,(3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl,(3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl,(3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl,2-azabicyclo[2.2.1]hept-5-enyl, 3-azabicyclo[3.1.0]hexanyl,(1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,(cis,cis)-3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.0]hexanyl,(1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,(1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl and2,8-diazaspiro[4.5]decanyl; heterocyclyl-amino-C₁₋₈alkyl, whereinheterocyclyl is selected from the group consisting of azetidin-1-yl andpiperidin-4-yl; (heterocyclyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, whereinheterocyclyl is selected from the group consisting of piperidin-3-yl andpiperidin-4-yl; (heterocyclyl,C₃₋₁₄cycloalkyl-C₁₋₈alkyl)amino-C₁₋₈alkyl,wherein heterocyclyl is selected from the group consisting ofpiperidin-3-yl and piperidin-4-yl;heterocyclyl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heterocyclyl is selectedfrom the group consisting of pyrrolidin-2-yl, piperidin-2-yl,piperidin-3-yl, piperidin-4-yl and tetrahydro-2H-pyran-4-yl; or(heterocyclyl-oxy-C₁₋₈alkyl,C₁₋₈alkyl)amino selected fromtetrahydro-2H-pyran-2-yl-oxy-C₁₋₈alkyl,C₁₋₈alkyl)amino.
 5. The compoundof claim 1, wherein R₆ is heteroaryl, wherein heteroaryl is selectedfrom the group consisting of 1H-tetrazolyl, imidazolyl, pyrrolyl and2H-tetrazolyl; or, heterocyclyl, wherein heterocyclyl is selected fromthe group consisting of azetidinyl, pyrrolidinyl, tetrahydrofuranyl,piperidinyl, piperazinyl, morpholinyl, 2,5-dihydro-1H-pyrrolyl,1,2,3,6-tetrahydropyridinyl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl,octahydro-6H-pyrrolo[3,4-b]pyridinyl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl,1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl,(3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl,(3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl,2-azabicyclo[2.2.1]hept-5-enyl, 3-azabicyclo[3.1.0]hexanyl,3,6-diazabicyclo[3.1.0]hexanyl, (1R,5S,6s)-3-azabicyclo[3.1.0]hexanyl,(1S,5R,6R)-3-azabicyclo[3.2.0]heptanyl,(1S,5R,6S)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl,2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl,2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl,2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl and2,8-diazaspiro[4.5]decanyl.
 6. The compound of claim 1, wherein R₆ isheteroaryl, wherein heteroaryl is selected from the group consisting of1H-tetrazol-5-yl, imidazol-1-yl, pyrrol-1-yl and 2H-tetrazol-2-yl; or,heterocyclyl, wherein heterocyclyl is selected from the group consistingof azetidin-1-yl, pyrrolidin-1-yl, tetrahydrofuran-2-yl, piperidin-1-yl,piperazin-1-yl, morpholin-4-yl, 2,5-dihydro-1H-pyrrol-1-yl,1,2,3,6-tetrahydropyridin-4-yl,hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl,(4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-4(4aH)-yl,(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl,5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl,octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl,(3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(1H)-yl,(3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,(3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,(3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-2(1H)-yl,1,3-dihydro-2H-isoindol-2-yl, octahydro-2H-isoindol-2-yl,(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl,(3aR,7aS)-octahydro-2H-isoindol-2-yl,(3aR,4R,7aS)-octahydro-2H-isoindol-2-yl,(3aR,4S,7aS)-octahydro-2H-isoindol-2-yl,2,5-diazabicyclo[2.2.1]heptan-2-yl, 2-azabicyclo[2.2.1]hept-5-en-2-yl,3-azabicyclo[3.1.0]hexan-3-yl, 3,6-diazabicyclo[3.1.0]hexan-3-yl,(1R,5S,6s)-3-azabicyclo[3.1.0]hexan-3-yl,(1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl,(1S,5R,6R)-3-azabicyclo[3.2.0]heptan-3-yl,(1S,5R,6S)-3-azabicyclo[3.2.0]heptan-3-yl, 5-azaspiro[2.4]heptan-5-yl,2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl,2,6-diazaspiro[3.4]octan-6-yl, 2,7-diazaspiro[3.5]nonan-2-yl,2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]decan-2-yl and2,8-diazaspiro[4.5]decan-2-yl.
 7. The compound of claim 1, wherein R₇ isC₃₋₁₄cycloalkyl, wherein C₃₋₁₄cycloalkyl is selected from the groupconsisting of cyclopropyl and cyclobutyl; C₃₋₁₄cycloalkyl-amino, whereinC₃₋₁₄cycloalkyl is selected from cyclopropyl; aryl, wherein aryl isselected from phenyl; aryl-C₁₋₈alkyl, wherein aryl is selected fromphenyl; aryl-amino, wherein aryl is selected from phenyl;(aryl,C₁₋₈alkyl)amino, wherein aryl is selected from phenyl;aryl-C₁₋₈alkyl-amino, wherein aryl is selected from phenyl;(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino, wherein aryl is selected from phenyl;(aryl-C₁₋₈alkyl)₂-amino, wherein aryl is selected from phenyl;aryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein aryl is selected from phenyl;(aryl-C₁₋₈alkyl,C₁₋₈alkyl)amino-C₁₋₈alkyl, wherein aryl is selected fromphenyl; (aryl-C₁₋₈alkyl)₂-amino-C₁₋₈alkyl, wherein aryl is selected fromphenyl; aryl-C₁₋₈alkoxy, wherein aryl is selected from phenyl;aryl-C₁₋₈alkoxy-carbonyl-amino, wherein aryl is selected from phenyl;heteroaryl, wherein heteroaryl is selected from the group consisting ofpyridin-2-yl, pyridin-4-yl, thiazol-2-yl and 1H-1,2,3-triazol-1-yl;heteroaryl-C₁₋₈alkyl-amino-C₁₋₈alkyl, wherein heteroaryl is selectedfrom the group consisting of pyridin-2-yl, pyridin-3-yl andpyridin-4-yl; heterocyclyl, wherein heterocyclyl is selected from thegroup consisting of pyrrolidin-1-yl and morpholin-4-yl;heterocyclyl-C₁₋₈alkyl, wherein heterocyclyl is selected frompyrrolidin-1-yl; or, heterocyclyl-oxy, wherein heterocyclyl is selectedfrom tetrahydro-2H-pyran-2-yloxy.
 8. The compound of claim 1, whereinthe compound of Formula (I) is a compound of Formula (Ia):

or a form thereof; wherein the form of the compound is selected from afree acid, free base, hydrate, solvate, clathrate, isotopologue,racemate, enantiomer, diastereomer, stereoisomer, polymorph or tautomerform thereof.
 9. The compound of claim 1, wherein the compound or a formthereof is selected from the group consisting of:5-benzyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)phenyl]-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-cyclohexyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-propyl-1,2-dihydropyridine-3-carboxylicacid5-cyclopropyl-6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-{4-[(2-hydroxyethyl)(methyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-[2-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-methoxy-2-methylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(2,4-dimethoxyphenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[2-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-(2,4,6-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-(2,3,4-trimethoxyphenyl)-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-[2-fluoro-4-(piperidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[2-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-methoxy-2-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[2-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[2-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-2-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-2-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[2-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[2-(dimethylamino)-4-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-2-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-3-methylphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-3-methoxyphenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[3-methoxy-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[3-methoxy-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[3-methyl-4-(pyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[3-methyl-4-(piperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-(4-fluorophenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-chlorophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-bromophenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-iodophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-{4-[(3-iodopropyl)amino]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(azetidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid 5-ethyl-6-{4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)-3-fluorophenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(dimethylamino)phenyl]-4-hydroxy-2-oxo-5-(propan-2-yl)-1,2-dihydropyridine-3-carboxylicacid6-[4-(diethylamino)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-[4-(pyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid6-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-(1H-imidazol-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-[4-(piperidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-[4-(2-oxopyrrolidin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-{4-[(3R)-3-hydroxypiperidin-1-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-(3-hydroxypyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-{3-[1-(dimethylamino)cyclopropyl]pyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[(3aR,5r,6aS)-5-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-{(3S,4R)-3-[(dibenzylamino)methyl]-4-methylpyrrolidin-1-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[(3aR,5r,6aS)-5-(benzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[(3aR,5r,6aS)-5-(dibenzylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[1-(tert-butoxycarbonyl)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(3-{[benzyl(methyl)amino]methyl}pyrrolidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-(4-hydroxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[4-(benzyloxy)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-(4-methoxypiperidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[4-(dibenzylamino)piperidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(4-aminopiperidin-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-{4-[3-(pyridin-2-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-{4-[3-(1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl]phenyl}-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-[4-(3-ethyl-3-hydroxypyrrolidin-1-yl)phenyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-[4-(3-hydroxy-3-methylpyrrolidin-1-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[3-(aminomethyl)-3-methylpyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[3-(dimethylamino)pyrrolidin-1-yl]-2-fluorophenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-{2-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-{2-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[di(prop-2-en-1-yl)amino]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-[4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-{4-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-2-methylphenyl)-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(2,5-diazaspiro[3.4]octan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-(4-(ethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-(methylamino)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(2-oxoethyl)-1,2-dihydropyridine-3-carboxylicacid6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-(2,3-dihydroxypropyl)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid(E)-6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-enyl)-1,2-dihydropyridine-3-carboxylicacid6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(hydroxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(dimethylamino)phenyl)-4-hydroxy-5-(methoxymethyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid6-(4-(dimethylamino)phenyl)-4-hydroxy-2-oxo-5-(prop-1-ynyl)-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-(4-(1-ethylpiperidin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-2-oxo-6-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1,2-dihydropyridine-3-carboxylicacid5-ethyl-6-(4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid5-ethyl-4-hydroxy-6-(4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid, and6-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid wherein the form of the compound is selected from a free acid, freebase, salt, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph or tautomer formthereof.
 10. The compound of claim 1, wherein the compound or a formthereof is selected from the group consisting of:5-ethyl-4-hydroxy-2-oxo-6-[4-(piperazin-1-yl)phenyl]-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate5-ethyl-6-{4-[(3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-[4-(7-amino-5-azaspiro[2.4]hept-5-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate5-ethyl-4-hydroxy-6-(4-{3-[(methylamino)methyl]pyrrolidin-1-yl}phenyl)-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-{4-[(3aR,4R,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-[4-(1,3′-bipyrrolidin-1′-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(3aR,4S,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-4-hydroxy-5-methyl-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride4-hydroxy-5-methyl-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(3aR,4R,7aS)-4-(dimethylamino)octahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(3aR,4R,7aS)-4-aminooctahydro-2H-isoindol-2-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate6-{4-[(3aR,4R,6aS)-4-(dimethylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate6-(4-{(3aR,7aS)-3a-[(dimethylamino)methyl]octahydro-2H-isoindol-2-yl}phenyl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-{4-[(3aR,4S,6aS)-4-(methylamino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-{4-[(3aR,4S,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-{4-[(1R,5S,6s)-6-(methylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[(1R,5S,6s)-6-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-[4-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-4-hydroxy-6-{4-[(3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride5-ethyl-6-{4-[(3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[3-(dimethylamino)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-[4-(3a-cyanooctahydro-2H-isoindol-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate6-[4-(1-amino-3-azabicyclo[3.1.0]hex-3-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-[4-(2,8-diazaspiro[4.5]dec-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-{4-[3-(2-aminopropan-2-yl)pyrrolidin-1-yl]phenyl}-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride6-[4-(2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl]-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid trifluoroacetate5-ethyl-4-hydroxy-6-{4-[(3aR,4R,7aS)-4-(methylamino)octahydro-2H-isoindol-2-yl]phenyl}-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride, and 5-ethyl-6-{4-[(3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl]phenyl}-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylicacid hydrochloride; wherein the form of the compound is selected from afree acid, free base, hydrate, solvate, clathrate, isotopologue,racemate, enantiomer, diastereomer, stereoisomer, polymorph or tautomerform thereof.
 11. A method of treating a bacterial infection in asubject in need thereof comprising administering an effective amount ofa compound of claim 1 to the subject, wherein the bacterial infectionresults from a bacteria of the phyla selected from the group consistingof Acidobacteria; Actinobacteria; Aquificae; Bacteroidetes; Caldiserica;Chlamydiae; Chlorobi; Chloroflexi; Chrysiogenetes; Cyanobacteria;Deferribacteres; Deinococcus-Thermus; Dictyoglomi; Elusimicrobia;Fibrobacteres; Firmicutes; Fusobacteria; Gemmatimonadetes;Lentisphaerae; Nitrospira; Planctomycetes; Proteobacteria; Spirochaetes;Synergistetes; Tenericutes; Thermodesulfobacteria; Thermomicrobia;Thermotogae; and Verrucomicrobia.
 12. The method of claim 11, whereinthe bacterial infection results from a bacteria of the phyla selectedfrom the group consisting of Proteobacteria, Spirochaetes,Bacteriodetes, Chlamydiae, Firmicutes and Actinobacteria.
 13. A methodof treating a bacterial infection in a subject in need thereof,comprising administering an effective amount of a compound of claim 1 tothe subject, wherein the bacterial infection results from a bacterialspecies selected from the group consisting of Acinetobacter baumannii,Bacillus anthracis, Bacillus subtilis, Enterobacter spp., Enterococcusfaecalis, Enterococcus faecium, Escherichia coli, Francisellatularensis, Haemophilus influenzae, Klebsiella pneumoniae, Moraxellacatarrhalis, Mycobacterium tuberculosis, Neisseria spp., Pseudomonasaeruginosa, Shigella spp., Staphylococcus aureus, Streptococcuspyogenes, Streptococcus pneumoniae and Yersinia pestis.
 14. The methodof claim 11, wherein the effective amount of the compound or a formthereof is in a range of from about 0.001 mg/Kg/day to about 500mg/Kg/day.
 15. A pharmaceutical composition comprising an effectiveamount of a compound of claim 1 or a form thereof in admixture with apharmaceutically acceptable excipient; wherein the form of the compoundis selected from a free acid, free base, hydrate, solvate, clathrate,isotopologue, racemate, enantiomer, diastereomer, stereoisomer,polymorph or tautomer form thereof.
 16. A combination therapy comprisingan effective amount of a compound of claim 1 or a form thereof and aneffective amount of an antibiotic or antibacterial agent; wherein theform of the compound is selected from a free acid, free base, hydrate,solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer,stereoisomer, polymorph or tautomer form thereof.
 17. The combinationtherapy of claim 16, wherein the agent is one or more selected from thegroup consisting of Ciprofloxacin, Enoxacin, Gatifloxacin, Levofloxacin,Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin and Ofloxacin.18. The combination therapy of claim 16, wherein the agent is one ormore selected from the group consisting of Amikacin, Amoxicillin,Ampicillin, Arsphenamine, Azithromycin, Azlocillin, Aztreonam,Bacitracin, Capreomycin, Carbenicillin, Cefaclor, Cefadroxil, Cefalexin,Cefalotin, Cefamandole, Cefazolin, Cefdinir, Cefditoren, Cefixime,Cefoperazone, Cefotaxime, Cefoxitin, Cefpodoxime, Cefprozil,Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxime,Chloramphenicol, Cilastatin, Clarithromycin, Clavulanate, Clindamycin,Clofazimine, Cloxacillin, Colistin, Cycloserine, Dalfopristin, Dapsone,Daptomycin, Dicloxacillin, Dirithromycin, Doripenem, Doxycycline,Erythromycin, Ethambutol, Ethionamide, Flucloxacillin, Fosfomycin,Furazolidone, Fusidic acid, Gentamicin, Imipenem, Isoniazid, Kanamycin,Lincomycin, Linezolid, Loracarbef, Mafenide, Meropenem, Methicillin,Metronidazole, Mezlocillin, Minocycline, Mupirocin, Nafcillin, Neomycin,Netilmicin, Nitrofurantoin, Oxacillin, Oxytetracycline, Paromomycin,Penicillin G, Penicillin V, Piperacillin, Platensimycin, Polymyxin B,Pyrazinamide, Quinupristin, Rapamycin, Rifabutin, Rifampicin, Rifampin,Rifapentine, Rifaximin, Roxithromycin, Silver sulfadiazine,Spectinomycin, Streptomycin, Sulbactam, Sulfacetamide, Sulfadiazine,Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine,Sulfisoxazole, Tazobactam, Teicoplanin, Telavancin, Telithromycin,Temocillin, Tetracycline, Thiamphenicol, Ticarcillin, Tigecycline,Tinidazole, Tobramycin, Trimethoprim, Troleandomycin and Vancomycin. 19.The method of claim 13, wherein the effective amount of the compound ora form thereof is in a range of from about 0.001 mg/Kg/day to about 500mg/Kg/day; wherein the form of the compound is selected from a freeacid, free base, hydrate, solvate, clathrate, isotopologue, racemate,enantiomer, diastereomer, stereoisomer, polymorph or tautomer formthereof.